Vincent Chase is a young, hot, up-and-coming actor living in Hollywood. Tonight, he must attend the opening of his latest movie "Head On," but first he and his three best friends from back home (Queens, NY) have lunch and discuss their upcoming 10-year high school reunion. Vince is reluctant to go but his buddies urge him to go with them. At the post-premiere party, Vince's agent, Ari, hassles Eric about getting Vince to read the script for a possible new project. Over breakfast, Vince says he's not going to do "Matterhorn" on Eric's advice. The foursome goes to meet with the director where Vince impresses him so much that Ari calls later to tell him that they've offered $4 million for the part. While Turtle and Drama celebrate, Vince lets him know that Eric is not too enthused about the script. Later, Ari and Eric share a rather confrontational dinner while discussing the future of their star's career. After Vince decides to take Eric's advice not to do the movie, the boys leave for their reunion. Before they can drive off, though, they get a call with some bad news: Colin Farrell has taken the part.

While Drama practices for his acting class over breakfast, Turtle enters with some bad news: an important trade magazine has given Vince's performance a negative review (including calling him a "fly-by-night pretty boy"). While paying Ari an office visit to discuss it, Eric meets Ari's new assistant, Emily. Following Ari's advice to show Vince a good time to get his mind off the review, Eric okays Vince's poor decision to lease a new Rolls Royce. Jessica Alba bumps into the boys during their luncheon and invites them to her party for Justine Chapin, her virginal pop-singer friend. The party proves to be a good time for everybody: Justine hits on Vince, Turtle shows off the Rolls to some girls, Eric gets some much needed assurance, and Drama finds that he isn't the only one skipping his acting class. In the morning, Eric reads Vince a review from the New York Times proclaiming him to be "the next Johnny Depp."

The boys attend a boxing match at the Staples Center where they bump into various celebrities. While Turtle and Drama talk up Luke Wilson about his new home theater system, Jimmy Kimmel invites Vince to come on his show to promote "Head On." In the morning, the foursome discuss their past relationships with women, and the consensus (all but Eric) seems to be that it's better to leave a girl dangling than break up with her. Drama also fills Vince in on his old grudge against Jimmy Kimmel. Later on, Eric tries his best to do a pre-interview for Vince's appearance while they all enjoy a game of golf. Afterwards, he breaks it to Vince that one of his one-night stands will be appearing on the show as well. The day of the show, Kristen stops by the guest house to pick up some things from Eric where the visit quickly turns into "break-up sex." Meanwhile, Drama and Turtle visit Rufus, who tells them that if Vince plugs his company on the show, they'll get their home theater system for free. At the show, the boys go to the Green Room while Vince finds sets out for a pre-show apology/visit. Emily shows up and shares a cigarette with Eric, and with a little help from Drama, their free home theater system is secured.

Ari wakes Eric with a phone call to remind him that tonight is the all-important opening night for Vince's movie. Immediately after Eric hangs up, Emily unexpectedly drops off fan mail, but with ulterior motives. Drama introduces the guys to his latest lady friend back at the house and then they discuss their plans for the evening over breakfast at a diner. Vince's major work for the day is a stop at Big Boy's Neighborhood, a local radio show. As a result of the appearance, Vince secures a date for himself with Justine Chapin. While everybody gets ready for the night's activities, Ari video conferences with Eric to tell him that matinée numbers for Vince's movie have been "less than stellar" because it is in direct competition with the latest Pixar feature. Kristen also calls to confess to Eric that she might still harbor feelings for him. Turtle resorts to desperate measures to get a date for their night of bowling, and it does not go unspoiled. After bowling, the large group makes a stop at a night club where, one by one, the boys find themselves alone. The night does not end on a bad note, however, and Ari arrives with some good news.

The boys are less than pleased that Vince's latest fling, Fiona, has overstayed the 3-day rule that Vince instated long ago. At the gym, her new age approach to exercise bothers Drama. Her vegan lifestyle seems to be bothering everybody in the house. Eric is re-introduced to an old acquaintance who may have just the script that Vince has been looking for: a story about a guy from Queens. Turtle tries to find a way around a weed drought in LA. Over lunch with Ari, Eric learns that the producer of "Queens Boulevard" doesn't like Vince. Fiona overhears Turtle's dilemma and offers to take the guys to her Sherpa. The Sherpa (played by Val Kilmer) happily treats them all to some of his organically grown, pesticide-free "herbal supplements" and gets a little paranoid when Eric's phone rings. Eric and Vince have dinner with Scott Wick, the movie's producer, thanks to Ari. It's not going very well until Vince offers to hook Scott up after admitting to being high during the meeting. The three share a joint in Scott's car when a cop stops by to check up on them but Vince's charm and movie-star status saves them all. Needless to say, Vince has left quite an impression, and he gets the part. The boys are all pleased when Fiona leaves for an extended trip to India.

The boys begin their day at Ari's office. They pair off: Drama prepares to meet his potential new agent and drags Turtle with him while Eric and Vince attend a special meeting. The "meeting" is basically an ego-booster for Vince where a roomful of agents try to entice him with potential projects. Drama discovers that his situation is an entirely different story when he finds his new agent answering his own phone in a cubicle. When he explains that it's going to be hard to find new jobs, an angered Drama storms out with some, ummm, dramatic parting words. Later, the boys attend Gary Busey's art opening where they bump into aspiring agent Josh Weinstein and a dejected Drama meets another old actor friend who is a waiter for a catering company. They leave the opening with an invitation to a hot beach party and go out with a bang, thanks to Turtle. Emily lets Ari know that he should be a little nervous about the whole situation. Turtle confronts Gary Busey with some interesting results. When Eric lets Ari know about their disapproval, Ari leaves his kid's birthday party to have an honest conversation with the pair. After things are settled, Ari lets Drama in on some somewhat surprising news.

Things appear to be back to normal. While the boys wait at a coffee shop for a meeting with Ari, they all give Eric a hard time about leaving Emily a drunken message the night before. Drama is in good spirits because he has some money to burn after getting residuals from his brief stint on "Pacific Blue". Ari has arranged a "meet & greet" with the director of "Queens Boulevard", so the group heads to the infamous Chateau Marmont. The outcome of the meeting is hazy: Vince likes Billy, but Eric is getting a bad feeling, and they walk away with a script that he has made revisions to. The revision that causes the most uproar begins to cause some tension among the ranks. Shauna lets Eric know that Vince's sex symbol status could be on the line if he chooses to go forward with this movie. Eric makes a secret phone call to Ari to express his concern. After hearing some reassuring wisdom, the boys screen Billy's previous film, which was a huge hit at Sundance. Amazingly, they all like it. The next day, handshakes are exchanged, and the decision is made to entrust the film to Billy Walsh.

Now Vince is about to return to New York for months to shoot, Turtle decides to make some money for a change- by charging entry for Vince's go away-party. Drama finds Adam Davies is a great agent, as he gets him a well-paid audition for a promising pilot, CSI Minneapolis to be shot in Vancouver starring Don Johnson whom Johnny already knows, interesting despite clashing with the timing for Queens Bouelevard and his temper flares up again. Meanwhile E insists he wants his work as Vince's manager recognized, with a formal contract, and plays it hard despite skepticism from Ari and, worst of all, Vince himself.