David and Paige Walling (Hugh Laurie, Catherine Keener) and Terry and Cathy Ostroff (Oliver Platt, Allison Janney) are best friends and neighbors living on Orange Drive in suburban New Jersey. Their comfortable existence goes awry when prodigal daughter Nina Ostroff (Meester), newly broken up with her fiance Ethan (Sam Rosen), returns home for Thanksgiving after a five-year absence. Rather than developing an interest in the successful son of her neighbors, Toby Walling (Brody), which would please both families, it's her parents' best friend David who captures Nina's attention.

When the connection between Nina and David becomes undeniable, everyone's lives are thrown into upheaval, particularly Vanessa Walling's (Alia Shawkat), Nina's childhood best friend. It's not long before the ramifications of the affair begin to work on all of the family members in unexpected and hilarious ways, leading everyone to reawaken to their lives, reassess what it means to be happy, and realize that sometimes what looks like a disaster turns out to be the thing we need.