This is my somewhat brief overview of Hughes' role in the anime, which is meant partially to inform, but mostly to show how bloody cool he is! Remember, for the full effect, you must watch the anime yourself! Also, be warned that there are free-range spoilers of the worst kind.
Hughes comes onto the scene in episode five, and of course from the very beginning he's on the phone to Roy, rambling on about his (then pregnant) wife. Of course, it's just a cover to make sure no one's tapping the line (or IS IT!? :O). But those are precautions that must be taken when the train has evil people on it who're planning to take the general onboard hostage! Though Hughes is too slick for them and manages to sneak to the outside of the train before they can catch him, and then helps Ed with the saving of the day.
In the next episode, Hughes goes to visit the Elrics at Tucker's place (where they are staying), because through his awesome investigative powers he learned that it was Ed's birthday. So he takes them back to his house for a party, but the festivities are cut a bit short when Gracia goes into labour! As there's a blizzard outside, Hughes runs to find a doctor while the brother's (and Nina) are left behind to deal with the woman in labour. Hughes returns with the doctor, and in true Hughes style cries rivers of tears of joy.
Hughes then spends the next episode investigating a serial killer, a certain cross-dressing Barry the Chopper. Good times. XD Though he still takes the time to flash about pictures of his family, of course!
The next four episodes are without Hughes, but our suffering is paid off by episode thirteen, where he returns with a bang! Ed gets called back to East Headquarters to be tested for the renewal of his license, and since he's such a brat, he challenges Roy to a fight for his exam. And of course, there's no one better to commentate then our dear Hughes (who came along with the Fuhrer when they temporarily took over East Headquarters, and right away started flashing about pictures of Elicia and bragging about his new promotion from Major to Lieutenant Colonel). And Hughes, being Hughes, takes the opportunity to show off a gigantic picture of Elicia to all those who are assembled, which the crowd doesn't exactly appreciate (the fools!), causing them to throw garbage and knock the picture over onto poor Hughes! *gasp!* He also takes the time to pass information on to Roy about the situation in Lior, and reveals that the real reason they're all at Easter Headquarters is Scar's rampage in Central.
Scar, being wily, follows them East, and causes quite a bit of havoc in episode 15. Of course, Hughes shows up after the fighting's done and over with! Afterwards, Hughes accompanies the Fuhrer back to Central, and the storyline follows the Elric brothers away from him. But before that happens, Hughes sees them off at the train station, passing on a message from Roy that it would be too much paperwork if they died, and telling them that they've determined that it was Scar who killed their friend Nina, thus giving Ed the will to fight Scar.
Hughes phones Roy in episode eighteen, partially to tell him about Scar's involvement in the destruction of the library and the rumours of Roy's return to Central, but mostly to brag about Elicia and harass Roy about getting married! Hughes then goes to pay a visit to Ed and Al, and because he was complaining about their inability to work on cases because of the destruction of the records in the library, Ed and Al introduce him to Sheska, who he hires immediately due to her ability to write out anything she's read, including the reports he needs. As Hughes leaves Sheska's house, Lieutenant Ross stops him and asks why he's only dispatching additional men to guard the library instead of sending the Elric brothers to work at headquarters where it would be safer, as they are still children and need protection. To that Hughes responds that he's doing that, because the Elric brothers are the only people who can do what they are doing right now, but as an adult he will watch over them as best he can.
Hughes then puts his new resource (Sheska) to work, having her endlessly copy out documents, and showing her pictures of Elicia to restore her energy when she gets tired. Because nothing restores pluck like the beauty of his daughter, in Hughes' mind. So cute!
A late-night phone call from Roy interrupts the pyjama-clad Hughes in episode twenty-two, because Roy is wondering why he and his crew haven't been in the series lately. But Hughes has more important things to worry about, as Armstrong, Ross, and Brosh are at his house to gain permission to investigate the 5th Laboratory, where those wacky Elric brothers ran off to. Hughes gives them the permission they seek, but warns them of the repercussions they might face for their actions. On their way, Hughes and friends run into King Bradley, who's trying to compete with Hughes for the cutest pyjama contest (but coming up short), who gives them more troops to go save the brothers and personally accompanies them. So for the first time in a while, Hughes sees some action, but sadly we don't get to see him in said action.
After investigating the remains of the 5th Laboratory, Hughes visits Ed and Al at the hospital in episode twenty-three, and tells them how the military is blaming Scar for all that happened, but asks Ed for the truth of what really occurred. After a moment, Ed gives in and tells him it was Homunculus, and that they had tried to make Ed create the Philosopher's Stone using people. After Ed's story, Hughes tells the boys to get some rest and leave everything to him, because Hughes is nice like that (so uncle-like)!
While going over papers, Hughes gets a call from Roy asking if there is any news (about Scar), but the only news Hughes has for him is the fact that it's Elicia's birthday the next day and Roy'd better get her a present, and that he'd tell Roy if anything about Scar comes up. After he hangs up, Sheska asks Hughes why he didn't tell Roy about what had happened, but Hughes decided Roy didn't need to know right then (he obviously didn't want to trouble his already troubled friend). He then assigns another long and arduous copying task to poor Sheska who just finished the last one.
Then, Hughes runs into Winry as she's leaving the Elric brothers' hospital room, and introduces himself and his daughter (by means of his ever-present photo of her). He asks if she'd like to meet Elicia, and when she gives a half-assed yes he takes it upon himself to take her home with him, rambling the whole way about Elicia's birthday and what Winry should get her (and Ed's birthday is mentioned as well, but we all know who Hughes obsesses over and it's not the world's shortest alchemist).
At Elicia's birthday party, Hughes comments on how Winry and Elicia look like sisters, and Winry tells him it would be nice to have a little sister as she has no siblings. But Hughes corrects her, and tells her that she does, because she has Ed and Al. Winry tells him if they were siblings, the boys would tell her more about what's going on, but Hughes corrects her again, saying how men use actions instead of words, and don't want others to worry or suffer. But in the end, she's the only person who they can show their weak sides. Gracia then interrupts their conversation with a birthday cake she made for Ed, and Hughes tells Winry she should go and see them. Winry reminds Hughes that he was going to give Ed a present, but Hughes tells her there are no presents better than Winry's smile. (Possibly he's just being his wonderful, uncle-like self, but one can't help but suspect he spent all his money on Elicia...)
Episode twenty-five begins with a flashback of Hughes visiting a somewhat bedraggled Roy, with the gift of an apple pie his girlfriend made. When Hughes sees that Roy was researching human transmutation he gets angry, but Roy tells him not to worry as he hadn't done anything. Roy mentions how many people died, but Hughes points out it was a war, to which Roy counters that Hughes wasn't there. Hughes tells him he should have requested a desk job like he had, and asks if he thought becoming a state alchemist and reviving the dead would help. When Roy replies that he doesn't know, Hughes punches him and asks if a taboo was so easy to commit he just needed a bit of research, or if what Roy really wanted was death. With a gun very visible on the table behind Hughes, he tells Roy there's an easier way. But Roy is afraid of dying, and knows even his life will have some use, and that he's decided...
And then Sheska wakes Hughes, who is sleeping at his desk. The Fuhrer has stopped by to see him, and takes Hughes back to his own office, where while his secretary sits and works. The Fuhrer wants to talk about how he seems to be investigating the high command of the military, to which Hughes admits he was doing, in relation to the incident at the 5th Laboratory. The Fuhrer tells him he had taken command of that case and found out that Brigadier General Basque Gran might have teamed up with some Ishbalites to conduct dangerous research. He asks Hughes if he is not satisfied with that conclusion, and Hughes, being his curious self, is not. When the Fuhrer mentions the Philosopher's Stone, Hughes tells him how he believes that within the military there had been research to create the stone which involved many illegal acts, and that Gran had not done it alone. Hughes then turns over the list of people he believes were involved. The Fuhrer tells Hughes that if it becomes known that there is a faction in the military that still wants to create the Philosopher's Stone, the military will lose its authority. But then smiles, says he's only kidding, and asks Hughes to investigate the matter fully. Then, when Hughes asks if he can ask Dr. Marco a few more questions on the matter, the Fuhrer tells his secretary to tell Hughes where the doctor is, as she is the only one who knows, for security reasons.
Hughes then goes and shares his findings with the Elric brothers, Winry, and Armstrong, while Brosh tries to listen in and Ross purposely tries to not hear. Hughes and Armstrong talk of finding the scientists who worked with Dr. Marco, but Ed and Al tell them they don't care about that anymore, as they decided to go ask their Sensei instead of dealing with dangerous things such as Homunculus and the Philosopher's Stone. Outside in the hallway, Brosh tells Hughes and Armstrong he's glad they gave up on getting involved in dangerous matters, but Hughes and Armstrong know that the brothers are just trying to avoid having people close to them become the next victims.
Gracia and Elicia join Hughes and other military personnel in saying goodbye to Ed, Al, and Winry at the train station.
Over the phone (as par usual), Roy gets mad at Hughes for not telling him the Elrics had been hospitalised, which Hughes then pretends to have forgotten to do, and passes it off as not that big of a deal. He then says how Roy's imminent transfer is more important, and how he should hurry up and rise in the ranks and get a wife. Roy, of course, hangs up.
While Hughes tucks in a sleeping Elicia, Gracia mentions that Roy seems to be worried about the two brothers as well, but Hughes sees no reason to worry him, and besides, he figures their line might be tapped. Hughes apologises to his wife, because he has something he still needs to investigate, and she tells him to be careful. He tells his sleeping daughter he has a lot of work to do, and kisses her goodbye.
Back at his office, Hughes runs Sheska ragged to find him papers on things such as the rebellions in Lior and Ishbal, and what was found in the 5th Laboratory. Of course, instead of getting overtime pay, she gets a picture of Elicia. Going through all the papers, he puts information about the Philosopher's stone, the rebellions, but it's only when he gets a phone call from the Fuhrer's secretary, who has the same name as the soldier who started the rebellion in Ishbal, Juliet Douglas, telling him the hotel where Dr. Marco is and that he can meet him tonight, that everything clicks into place.
Hughes immediately orders Sheska to return all the books and then go home, and then runs from his office, firing her on his way out, telling her to never come there again.
At the hotel, Hughes asks Miss Douglas if she's heard of the Ishbal war, which she replies she hasn't, and he goes on saying how he found out that a soldier with the same name started the war, to which she replies it's a common name. He then tells her that the soldier was reported as dead two years before the rebellion, but the name was never removed from the list, and received a promotion in the past two years, to which she replies that the soldier was selected to be the Fuhrer's secretary. Hughes asks who she is, but she just replies that the doctor is waiting.
As Hughes goes to open the door Marco is supposedly behind, Lust bursts out of the one across the hall and attacks him. Hughes tells her she has a cool tattoo, then dodges her attack (though she still manages to slash his arm) and throws one of his knives right between her eyes. Suddenly Lieutenant Ross appears and shoots at Lust, giving Hughes even more time to escape, and the two run from the hotel.
Hughes tells Ross that the enemy has infiltrated the military, but stops himself before he tells her any more. She follows him to a payphone, where in his rush to find change he drops a picture of himself with his family and it falls to the ground in front of Ross. But Roy isn't there when Hughes calls, because he had left for Central that day. Hughes hangs up, and Ross tells him they should head to a safe place. Hughes agrees, but when Ross turns her back to him he calmly puts one of his knives against her throat and tells her to tell him some things, because the real Lieutenant Ross has a mole under her eye. Fake-Ross then makes a mole magically appear, which Hughes calls amazing, right before he slits her throat, then asks for her forgiveness but he has a wife and child waiting at home.
Sadly, that isn't enough to stop Envy, and he gets back to his feet, transforming from Ross into Gracia. Hughes turns to attack when he hears the sound, but faced with the woman he loves he hesitates, and Envy shoots him.
It takes a moment for Hughes to fall, and once he finally does Roy's voice is heard, continuing the flashback from the beginning of the episode. Roy vows to become Fuhrer, and change the country. Hughes replies that he'll need someone to understand and support him, and that he'll work under Roy and help him climb to the top. And in the present, Roy rides the train to meet Hughes, unaware of what happened.
A solemn crowd gathers as Hughes' casket is lowered into the ground, and Elicia doesn't understand why they're burying her daddy when he has so much work to do and becomes more and more frantic. All Gracia can do is hug her daughter and cry. The site also causes Armstrong to break down, but Roy manages to remain stoic. Long after everyone has gone, Roy remains, and ponders the absurdity of the man who would support him from beneath having been promoted above him to Brigadier General after his death. When Hawkeye approaches, he tells her how he had previously developed a theory on human transmutation, and was trying to remember it. He also wonders why Hughes never told him if the Elric brothers were involved, and Hawkeye wonders if it was for Roy's own good, as Roy has trouble remaining in control when the Elric brothers are involved. Roy puts on his hat, and makes an off-hand remark about how it is starting to rain. Hawkeye knows it is only Roy's tears, but agrees with him anyway.
On the train, Ed and Al eat an apple pie Gracia baked for them, and discuss Hughes, and how he would always visit, and wonder why he cared so much for them. Winry tells them they'd better say thanks to him when they return to Central. As they pass a train station, for a minute Ed can see a spectre of Hughes waving to them.
But even after his death, Hughes is still present in the series, if only in those who love him. Sheska goes on her own personal mission to discover why he died, while Roy does nothing when he obviously wants to. Plus there's the fact that up until episode 44 everyone's making sure to not mention to the Elrics that Hughes was murdered, and then Ed's explosive reaction when he finds out. See, I'm not the only one who loves Hughes.