Ned (PAUL RUDD) is heavily-bearded and amiable but not always terribly bright organic farmer who feels bad for a cop asking for pot and thus sells him some, unaware that it's a sting operation. After serving time in jail, Ned is released and returns to the farm only to discover that his girlfriend, Janet (KATHRYN HAHN), has ditched him in favor of her new live-in boyfriend Billy (T.J. MILLER). To make matters worse, she won't let him take his dog, Willie Nelson, with him when she kicks him off the farm.
As a result, and after checking in with his parole officer, Omar (STERLING K. BROWN), Ned moves back in with his mom, Ilene (SHIRLEY KNIGHT), before alternating home-crashing with his three adult sisters. First up is Liz (EMILY MORTIMER), a frumpy stay-at-home mom raising two kids while her husband, Dylan (STEVE COOGAN), is getting mighty close to Tatiana (LYDIA HAUG), the ballerina subject of his latest documentary. Ilene and Dylan are extra protective of their kids, including 7-year-old son River (MATTHEW MINDLER), and thus don't appreciate Ned trying to expose the boy to new and what they believe are bad and/or potentially harmful things.
When that doesn't work out, Ned goes to live with Miranda (ELIZABETH BANKS), a bossy journalist who's hoping to get her big break by getting the scoop on Lady Arabella (JANET MONTGOMERY), especially after Ned befriends and gets her to open up -- off the record -- about her life as a royal. When she isn't busy with that, Miranda is often bossing around her neighbor, Jeremy (ADAM SCOTT), who puts up with her behavior since he has a secret crush on her.
Finally, Ned also moves in with his third sister, Natalie (ZOOEY DESCHANEL), a bisexual woman who lives in a loft with many other people, including her lawyer girlfriend, Cindy (RASHIDA JONES); tries her hand at stand-up comedy; and occasionally poses nude for artist Christian (HUGH DANCY).
When he's not trying to get his dog back, Ned's straightforward and non-filtered approach to life and speaking about things the way he sees them ends up rubbing all of his sisters the wrong way, but ultimately results in them changing those things in their lives that weren't working for them.