Matthew "Matt" King (George Clooney) is a Honolulu-based attorney and the sole trustee of a family trust that controls 25,000 acres of pristine land on the island of Kauai—land that is not only of great monetary value, but of distinct cultural value as well. Though he has been able to manage his money, most of Matt's cousins are broke from squandering their share of the inheritance. The trust will expire in seven years because of the rule against perpetuities, so the King family has decided to sell the land to Kauai's native Don Holitzer for development. Just before family members are ready to formally endorse the deal, a boating accident near Waikīkī renders Matt's wife, Elizabeth, comatose.
The Kings have two daughters, 17-year-old Alex (Shailene Woodley) and 10-year-old Scottie (Amara Miller). With Elizabeth in a coma at Queen's Hospital, he is forced to confront Scottie's inappropriate behavior with other children and Alex's destructive ways. Matt is informed by one of his wife's doctors that Elizabeth will never awaken from her coma, which means that under the terms of her living will she must be disconnected shortly from life support. When Matt tells Alex the news, she reveals that Elizabeth was having an affair at the time of the accident, which has caused a major rift between mother and daughter.
One of Matt's friends, Kai Mitchell, says that Elizabeth had planned to leave Matt for her lover; later, Kai's husband, Mark, tells him that the man is named Brian Speer (Matthew Lillard). Matt decides to find Brian and convince him to visit Elizabeth while she is still alive, learning that he is a real estate agent currently vacationing in Kauai. After telling the family of Elizabeth's terminal prognosis, Matt, along with the girls and Alex's slacker friend Sid (Nick Krause), travel to Kauai. During a jog on a beach, Matt recognizes Brian and follows him to a cottage owned by Matt's cousin, Hugh (Beau Bridges). Hugh tells him that Brian is Holitzer's brother-in-law, and if Matt and his family sell their land to Holitzer, Brian stands to gain a lot of money from commissions when it is developed.
Later that evening, Matt and Alex return to Brian's cottage and, while Alex distracts Brian's wife Julie (Judy Greer), Matt finally confronts Brian and tells him about his wife's condition. Brian says that while Elizabeth loved him, the affair was only a fling for him, and he loves his wife and family. He tells Matt he is sorry for the pain he caused.
Matt, Scottie, Alex and Sid return home. At Matt's request, at the hospital, Scottie is finally told of her mother's impending death by a grief counselor, allowing her, too, to begin her process of farewell.
After Elizabeth is disconnected, her father, Scott (Robert Forster), together with his wife and son, comes to the hospital to say his last goodbyes. He accuses Matt of not having been a more generous and loving husband to Elizabeth, whom he describes as a good and faithful wife. Matt agrees with him, choosing not to disclose the details of her affair. Sid and Alex both unexpectedly come to Matt's defense.
Matt meets with his cousins to vote on the fate of the land. The majority vote in favor of selling to Holitzer, but Matt has second thoughts and decides to keep the land and find a different solution. Shocked, Hugh tells Matt that he and the other cousins may take legal action, but Matt is undeterred.
Brian's wife Julie, after learning of the affair and realizing that Brian will not visit Elizabeth, comes to the hospital, partly feeling that decency obliges her to. She tearfully admits to Elizabeth that she wants to hate her for "trying to destroy" her family, but that she forgives her.
Alone by his wife's hospital bed after Julie leaves, Matt finally comes to terms with his wife's act of treachery, and tenderly kisses her goodbye. He is followed by Alex and Scottie.
Matt, Alex, and Scottie scatter Elizabeth's ashes in the ocean off Waikiki. The film closes in a "breaking the fourth wall" fashion, with the three watching the same screen as the film's viewers. The family settles in one at a time, ostensibly watching March of the Penguins, while curled up on the living room couch, eating ice cream and sharing the quilt that was on Elizabeth's death bed.