Living separate lives on opposite sides of the country, estranged siblings Maggie (Kristen Wiig) and Milo (Bill Hader) are at the end of their ropes. But after a moment of crisis reunites them, Milo goes to spend time with Maggie in the small New York town where they grew up. A dental hygienist, Maggie struggles with her unhappy marriage to the painfully good-natured Lance (Luke Wilson), while Milo tracks down Rich (Ty Burrell), the English teacher with whom he shares a checkered past. Adrift and wondering how they ended up so far from who they were supposed to be, the siblings try to patch things up.