Seven years ago at LAX, recent college graduate Oliver Martin (ASHTON KUTCHER) spots Emily Friehl (AMANDA PEET) get dumped by her boyfriend. The two end up on the same plane bound for New York, during which they have a tryst in the lavatory. She's headed for Manhattan to see her dad and stepmom, while he's visiting his deaf brother, Graham (TY GIORDANO), who's in law school. The two spend the day together and then go their separate ways, with the joke being that she'll call his parents in six years and see if he's married or still living at home with them and his younger sister Ellen (TARYN MANNING).
Three year's later, Emily is an actress whose friends, including Michelle (KATHRYN HAHN) and Gina (ALI LARTER), think she needs a date for New Year's Eve following her boyfriend breaking up with her. On a whim, she decides to call Oliver -- who's starting a business selling diapers over the Internet with his business partner Jeeter (KAL PENN) -- and the two briefly hook up, before going their separate ways again.
Over the next several years, the two repeatedly find or run into each other. As they discover that the other is either in or just out of a relationship, Oliver and Emily eventually become aware that perhaps they're meant to be together.