Ben Baker is a man-child who lives on his friend's couch getting high. His friend, Steve Dallas, is a moderately successful weather reporter who is living a superficial life. When Ben receives word that his father has died, Steve drives him home and they re-connect with Ben's successful and driven sister Terri and hippie step-mother Angela who is the same age as they are. The reading of the will drives Ben to come up with a new purpose in life, but those around him don't prove to be very supportive, and then they all re-examine their own life.

Growing up together, Mitch (Ryan Reynolds) and Dave (Jason Bateman) were inseparable best friends, but as the years have passed they've slowly drifted apart. While Dave is an overworked lawyer, husband and father of three, Mitch has remained a single, quasi-employed man-child who has never met a responsibility he liked. To Mitch, Dave has it all: beautiful wife Jamie (Leslie Mann), kids who adore him and a high-paying job at a prestigious law firm. To Dave, living Mitch's stress-free life without obligation or consequence would be a dream come true. Following a drunken night out together, Mitch and Dave's worlds are turned upside down when they wake up in each other's bodies and proceed to freak out. Despite the freedom from their normal routines and habits, the guys soon discover that each other's lives are nowhere near as rosy as they once seemed. Further complicating matters are Dave's sexy legal associate, Sabrina (Olivia Wilde) and Mitch's estranged father (Alan Arkin). With time...