Growing up together, Mitch Planko and Dave Lockwood (Ryan Reynolds and 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 children, 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 McArdle (Olivia Wilde) and Mitch's estranged father, Mitch, Sr. (Alan Arkin). 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.