Despite being 39-years-old, Brennan Huff (WILL FERRELL) still lives at home with his mom, Nancy (MARY STEENBURGEN), unlike his boastful and charismatic brother, Derek (ADAM SCOTT), who's V.P. of a helicopter leasing company and has two seemingly perfect kids with his wife Alice (KATHRYN HAHN).
Dale Doback (JOHN C. REILLY) is 40-years-old and similarly still lives with his doctor dad Robert (RICHARD JENKINS). When Nancy and Robert meet at a medical convention and instantly fall in love, that leads to their wedding and her moving into his house.
Of course, that means Brennan moves in as well, much to the chagrin of Dale who isn't happy to have a new stepbrother. The two immediately clash and act like bratty children, especially when they're forced to share the same bedroom, quickly get on Robert's nerves, while Nancy initially tries to take a more tolerant view of the new arrangement.
Dale and Brennan find a common foe, however, in Derek who isn't above belittling both of them. From that point on, and as Brennan becomes enamored with his therapist, Denise (ANDREA SAVAGE), and Dale has unhappily married Alice coming on to him, the two men must contend with the various changes in their lives that stem from their new familial arrangement.