Lifelong friends Dave and Mitch are envious of the other's life. Mitch thinks Dave has it all: a beautiful, loving family and a high-paying job at a prestigious law firm. But Dave thinks Mitch’s stress-free playboy life without obligation or consequence is the real dream come true. One fateful drunken night, they both admit that they wish they had the other’s life while peeing in a fountain when lightning strikes. The next morning, they wake up, hungover, in each other’s bodies! With time not on their side, Mitch and Dave comically struggle to avoid completely destroying each other’s lives before they can find a way to get their old ones back.

Roger Greenberg, a failed musician now making a living as a carpenter in New York, returns to Los Angeles to house-sit for his brother. He's stranded there—since he doesn't drive—until his brother's assistant, Florence, comes to his rescue. She's as much a lost soul as he is, and the pair form a significant connection—giving Roger a much-needed reason to be happy.

Larry Guthrie, who loses his first love to the town hot shot, decides to win her back by volunteering with the children at her after-school program. When Larry accidentally tells the kids the Tooth Fairy is make-believe, he soon is transformed into a tutu-clad fairy with the "sentence" of collecting teeth.