NOTE: This spoiler was submitted by John L

George Simmons (Adam Sandler) is a former standup comedian whose career bears a strong resemblance to Adam Sandler’s own. Simmons has starred in a series of highly profitable but extremely silly movies (in one “Splash”-like comedy, he played a mer-man; in another, resembling “Little Man,” he played a baby with an adult’s head).

During a visit with his doctor, Simmons learns that he has an advanced case of leukemia, too advanced for conventional treatments to help. He is given new, experimental drugs, but is warned that there’s only about an 8% chance that they will keep him alive. George goes back to his mansion, where it becomes clear that, despite his great wealth, he’s isolated, lonely and has no true friends.

He makes a phone call to Laura, a woman he loved many years ago and tries to apologize to her for ruining their relationship. She doesn’t seem interested in talking to him, and he hangs up after an awkward conversation.

Meanwhile, Ira Wright (Seth Rogen), an aspiring standup comedian, is working at the counter of a delicatessen, where he must bribe co-worker Chuck (rapper RZA)  to come to his performances at a local comedy club. Ira shares an apartment with friends Leo, a fat, bespectacled aspiring comedian, and Mark, an actor. Mark is currently earning big paychecks as the star of a TV sitcom called “Yo, Teach!” (think of “Head of the Class”), and his success is galling to Ira. More importantly, Mark is beginning to romance Daisy, a pretty neighbor (a standup comedian in her own right) whom Ira has long had a crush on, but has been too insecure to approach. Mark threatens to sleep with Daisy in ten days, if Ira doesn’t get up the nerve to ask her out himself.

Ira and Leo are both performing during Open Mike night at a comedy club. Leo gives a solid performance and wins some laughs. Just before Ira is to take the stage, he’s informed that his set has been delayed, because George Simmons has come to the club and wants to do a standup routine. The gloomy, depressed Simmons gives a downer of a performance, and the audience responds with uncomfortable silence. That’s a tough act to follow, and Ira’s own set gets off to a poor start. His own act relies heavily on jokes about farts and his penis, and he seems to be bombing. Ultimately, Ira salvages his act by making insulting jokes about George Simmons.

Ira encounters Simmons later in the club’s parking lot, where Simmons’ deluxe truck is preventing Ira from getting into his own car. When Ira tries to get George to move his truck, George pulls out and pretends he’s going to run Ira over, before speeding off.

The next day, George phones Ira and says he think both Ira and Leo are funny, talented guys, and asks if they can write jokes for him, as he’s planning to do a lot more standup comedy. Ira accepts the offer immediately, but lies and says Leo wouldn’t be interested. He never even tells Leo about the offer.

George has been hired to perform at a corporate function sponsored by Ira writes a funny set of computer-themed jokes for George, and joins him in a limousine and a chartered private jet to attend the function, which features singer James Taylor (playing himself) as the opening act. At the last minute, George sends Ira on stage to warm up the audience for him. Unprepared, Ira gives a successful performance, during which he uses many of the jokes he’d written for George.

In spite of this, George’s set is a hit. He gives Ira $1500 in cash, and hires him as a personal assistant. Ira will write jokes for George, but will also serve as gopher and all-around errand boy. Among other things, Ira must sit by George’s bedside each night and talk to him for some time, before George goes to sleep. During these conversations, each reveals secrets about himself. Ira comes from a broken home, and his real last name is Weiner (something that brought him a lot of mockery as a child). George is estranged from his family, because his father was an abusive alcoholic. Young George learned to be funny because making his father laugh sometimes saved him from a beating.

Despite his illness, George is still promiscuous and still seemingly irresistible to women. George brings home a pair of beautiful women, and has sex with both of them, while Ira blows his opportunity to score with either of them through his silliness and immaturity.

Ira is one of the only people to whom George reveals his medical condition. Ira helps George take his medicines, and sits patiently in the bathroom with George, as he experiences nausea from the medications. George shares intimate details of his life with Ira, including his tragic breakup with Laura, the love of his life, twelve years ago. George loved Laura more than any woman he’d ever known, but his repeated infidelity drove her away. George’s treatment of Ira varies constantly- sometimes, he treats Ira as his best friend, while other times, he coldly and cruelly treats Ira like a mere flunky

Ira can’t take the pressure of being the only one who knows how sick George is, so he urges George to tell other people and try to make amends for past bad behavior. The results vary. George gets together with some of his old friends from the world of comedy (Paul Reiser, George Wallace, Charles Fleischer, and others, playing themselves), who try to cheer him up. However, George fails miserably in his attempts to reconcile with his sister, who remains bitter and angry that George cut her and her children completely out of his life.

Ira also accompanies George on visits to his oncologist, a long-haired, blond Swede named Dr. Lars. During visits, Ira and George repeatedly tease the doctor for his foreign accent, comparing his appearance to one of the villains in “Die Hard” and making comical allusion to IKEA.

One night, Ira returns home early and find that his roommate Mark has had sex with Daisy, the girl of his dreams. Ira is enraged at both, but Mark points out that he waited nearly three weeks, long past the ten days he’d originally promised. And Daisy defends herself, noting that she had no obligation to be faithful to Ira, whom she’d never even dated yet.

Since George has no other friends, he comes to Thanksgiving dinner with Ira, Leo, Mark, and some of their friends, including Daisy. Before dinner, George Simmons gives a sad toast, and warns the young people gathered never to cherish the good times they share with friends, and never to let those friends slip away. Afterward, Ira ingratiates himself with Daisy by apologizing and acknowledging that she owed him nothing, as he wasn’t even her boyfriend. However, George causes a rift between Ira and roommate Leo when he inadvertently lets it slip that he’d wanted Leo to write jokes for him, too. Leo angrily denounces Ira for keeping him in the dark and keeping a great opportunity for himself alone.

At home, George receives a phone call from his ex-girlfriend Laura, who is now much warmer and kinder, since she knows George may be dying. She even offers to talk him to sleep the way she used to, this time over the phone.

Sometime later, Dr. Lars summons George to the hospital, and shares good news: the experimental medicines have worked, and George leukemia is now in remission. George gleefully shares the news with Ira, and feels he’s been given a new lease on life. He accepts a comedy gig in San Francisco, where Laura is now living with her family. He invites her to the show, and she accepts. She meets him backstage, and sits in the front row. When they meet and embrace, it’s clear they still have strong feelings for each other, after all these years. George is afraid to tell Laura that his illness is in remission, so he asks Ira to tell her.

The day after the show, both George and Ira visit Laura’s luxurious home, which she shares with her Australian husband Clarke (Eric Bana) and their daughters Mabel and Ingrid (played by director Judd Apatow’s real daughters, Maude and Iris). Laura confesses that the man she married is much like George, in that he’s unfaithful to her and is rarely home. George and Ira spend hours playing with Laura and her daughters. That afternoon, Laura and George pretend to go grocery shopping, leaving Ira to watch the girls, then slip off together to the guest house and have sex. While they’re away, the girls ask Ira if George is going to die. Ira reassures them that George’s disease is cured and that he’s going to be fine.

George and Laura return to the main house, without groceries, and suggest sending out for pizza. When a car comes to the door, they’re expecting it to be the pizza delivery boy. In reality, it’s Laura’s husband Clarke, who’s come home unexpectedly. Clarke believes that George is dying, and therefore shows his guests great warmth and hospitality. He urges them to stay in his guest house overnight, rather than drive 8 hours overnight back to Los Angeles.

In the guest house, Ira tells George how wrong it is to romance a married woman, and to endanger a happy family. George angrily dismisses Ira’s concerns, and condescendingly sends Ira to get him a Diet Coke.

The next day, as George and Ira are preparing to leave, Mabel and Ingrid tell their father that George’s illness has gone, and that he isn’t dying. This infuriates Clarke, who is now suspicious of his wife’s relationship with George. Laura and Clarke fight bitterly, each accusing the other of infidelity, which leads Clarke to drive off in a rage. With Clarke seemingly gone, Laura and George begin to make tentative plans to be together again. Clarke is planning to fly back to China on business that night. Laura intends to meet him at the airport and tell him their marriage is over.

However, now that a renewed relationship is a real possibility, George begins to pull away from Laura. Later,  when Laura shows both Ira and George a video of young Mabel singing “Memory” from the Broadway musical “Cats,” Ira finds the video delightfully earnest and touching, while George immediately goes in to insult comic mode and  begins mocking the girl’s performance.

Ira realizes that George can never be a good family man, and sees how sad Mabel and Ingrid are about their family’s looming breakup. When Laura goes to the airport to meet Clarke, Ira follows her, hoping to stop her from ending her marriage. As it turns out, that’s unnecessary. When Clarke and Laura see each other, he tearfully apologizes for being unfaithful and for being away from home so much. He pledges to get a job closer to home and to be a better husband.

Suddenly, Clarke sees Ira lurking in the airline terminal, which angers and confuses him. Clarke races back to his house to confront George, with Laura and Ira in hot pursuit. Clarke finds George, who attempts to flee. Clarke chases him down and begins to pummel him. When Ira arrives, he enters the fight on George’s side, and gets clobbered himself. At last, Laura manages to end the fight, getting Clarke to go inside, and telling George that she’s determined to keep her marriage and family together. Ira and George have to drive back to Los Angeles in the dark.

Ira and George’s friendship and partnership are over, seemingly forever. George believes Ira has destroyed his last chance at love by sabotaging his relationship with Laura. He cruelly tells Ira that he’s a loser and that he’ll never succeed as a comedian because he just isn’t funny. Ira tells George that he’s a selfish jerk, and that he’ll NEVER have a happy relationship because he’s incapable of loving anyone. George tells Ira “You’re fired,” and they have nothing more to say to each other. George drops Ira off at the apartment he shares with Mark and Leo, and drives off.

Ira returns to his old job at the delicatessen counter, starts dating Daisy seriously, and begins performing at comedy clubs again. This time, he shows much more confidence as a performer, and his material shows a bit more maturity and self-awareness. George Simmons is in the audience, not laughing, but paying close attention.

The next day, George visits Ira at the delicatessen and asks to have a word with him. They sit down together, and George pulls out some notes he’d taken while watching Ira’s standup performance. George admits that Ira’s personal criticisms of him were on the mark, and tries to make amends by offering some pointers and ideas for new jokes. Ira laughs at some of George’s ideas, admits they’re very good, and the two begin brainstorming, trying to come up with new jokes.

George and Ira may become real friends yet.