In 1978, five friends win their junior high basketball championship. During the celebration, their coach "Buzzer" (Blake Clark) encourages them to live their lives in a similar way to how they played the game.

30 years later, the five friends have since separated. Lenny Feder (Adam Sandler) is a high powered Hollywood talent agent who is married to Roxanne (Salma Hayek), a fashion designer. Together, they have two sons, Greg and Keith, and one daughter Becky, all of whom have become spoiled, much to Lenny's annoyance. Eric Lamonsoff (Kevin James) is now a co-owner of a lawn furniture company (but he says he is just to impress his friends) who is married to Sally (Maria Bello). Together, they have one daughter, Donna and one son Bean, who still breastfeeds despite being four years old, much to Eric's chagrin. Kurt McKenzie (Chris Rock) is a stay at home father who is married to Deanne (Maya Rudolph), the primary breadwinner of the family. Together, they have a son, Andre, and a daughter, Charlotte, while Deanne is pregnant with a third child, and her mother, Ronzoni, lives with them as well. All of them harass Kurt for not being more useful. Rob Hilliard (Rob Schneider) is a thrice divorced pacifist vegan married to Gloria (Joyce Van Patten), who is 30 years older than him. Marcus Higgins (David Spade) has become a single womanizer.

When they learn that their coach has died, they all return to New England with their families for the funeral. Lenny rents the lake house for the 4th of July weekend for his friends to stay at, but Lenny can't stay for the whole weekend because Roxanne has a fashion show in Milan. While at the lake house, Lenny is annoyed that their kids would rather play video games than spend time outdoors, so he and the others force their kids to spend more time outside while at the house.

At a local restaurant, Lenny runs into his old nemesis Dickie Bailey (Colin Quinn), who works as a cook there. Dickie is still upset at Lenny because he allegedly had his foot out of bounds when he made the long-ago game winning shot and challenges him and his friends to a rematch, but Lenny declines, declaring it a waste of time. During dinner, the group discusses spreading the coache's ashes in the morning, but Lenny says he can't be there because of Roxanne's fashion show. Roxanne angrily storms off because Lenny painted her negatively. She allows him to spread the ashes, but demands they leave early the following morning.

In the morning, the five guys row out to an island to spread the ashes. When Rob is spreading the ashes, he breaks down and tells the guys that he screwed up his previous marriages and that he's nervous about meeting his daughters who are coming. When they get back to the house, they finally meet Rob's daughters, two of them, Jasmine and Amber, who seem too gorgeous to be Rob's, and one, Bridget, who very closely resembles him. To calm his nerves, the five guys play a game called "Arrow Roulette", in which an arrow is shot up into the air and the last person who runs away wins. Rob wins, but the arrow lands in his foot.

That evening, when Roxanne is packing, Becky's tooth falls out, but Roxanne is too busy to notice and she tells her that she'll put a dollar under her pillow later. When Becky asks why she would do it instead of the Tooth Fairy, Roxanne tells Lenny that she's worried that she ruined Becky's childhood. When Lenny hears his kids supposedly talking on their cellphones, he comes into their bedroom to find them actually talking on "cup phones" with the other kids. Happy that the kids are starting to have the same kind of fun he did at their age, he asks everyone to install cup phones around the house. Roxanne then tells Becky through the cup phone the truth about the Tooth Fairy.

In the morning while packing the car, Roxanne sees all the kids having fun down by the lake and decides that they can't leave the lake house. Happy with his wife's new attitude, Lenny decides they should head to a waterpark for a day. There, Bean learns to drink milk out of a carton, while Marcus flirts constantly with Jasmine and Amber, much to Rob's dismay. The group run into Dickie again, this time with one of his friends Wiley (Steve Buscemi), who ends up in the hospital after a zip line accident.

Back out the house, Deanne becomes suspicious of Kurt when she sees him spending time with Rita, Lenny's nanny. That evening, the adults spend time together drinking and dancing, while reminiscing about their pasts. In the morning, Rob suspects that Marcus had sex with either Jasmine or Amber or both of them and confronts him. Jasmine and Amber assure him that he didn't and Marcus assures him that he never would. Roxanne then confronts Lenny about the fact that he canceled their Milan plane reservations before the funeral behind her back. Lenny claims that he felt their time at the lake house was necessary because their kids were becoming too spoiled, but was unsure if Roxanne would go along with it. He tells her he won't lie to her again. Deanne confronts Kurt about supposedly flirting with Rita. Kurt assures her that he wasn't flirting with her, but he enjoyed having an actual conversation with her because he doesn't feel like he gets that with Deanne. Deanne offers to take him out on more dates. Eric then admits to the group that he isn't co-owner of a lawn furniture company and that he was laid off two months ago. He just didn't want everyone to think of him as a failure. Lenny resolves to offer Eric an investment opportunity. Gloria then tells everyone that despite their recent hostility, she senses love between everyone.

The group then head off to a 4th of July barbecue, where they are once again challenged by Dickie and his friends to a rematch of the basketball game. Wiley, in a massive body cast, had escaped intensive care to watch. Rob suggests that their coach would want them to take the challenge and despite everyone's being out of shape and Rob's injury, they agree to a game. The game is close, but most of the players get too tired to continue, leaving only Lenny and Dickie on the court. They bring out their sons to continue playing. When Lenny has the chance to make the game winning shot, he deliberately misses and allows Dickie to win, giving him a sense of victory. Lenny and the others take the loss in stride.

While watching the fireworks, a drunken Marcus decides to play another game of Arrow Roulette, causing everyone to run away, except for Wiley, who can't move, and the arrow lands in his foot and he passes out as the movie ends.