Cast
Owen Wilson as Kyle Reynolds, Peter's fraternal twin brother. A laid-back model who made millions by selling his image to a BBQ sauce company, he is resented by Peter for his life being so easy.
Ed Helms as Peter Reynolds, Kyle's fraternal twin brother and a proctologist. He is divorced and facing a mid-life crisis because his teenage son Ethan hates him. Having never known his own father, Peter is unsure of how to deal with his son, inspiring him to attempt to find his biological father.
Glenn Close as Helen Baxter, Kyle and Peter's eccentric mother who is revealed to have been heavily sexually active in the mid-1970s and appears not to know who the twins' biological father is.
Annie Starke as young Helen Baxter
Christopher Walken as Dr. Walter Tinkler, a veterinarian and family friend who is one of the potential fathers of Kyle and Peter.
J. K. Simmons as Roland Hunt, a former financial investor in New York, reclusive criminal, and one of the potential fathers of Kyle and Peter.
Katt Williams as an unnamed hitchhiker who Kyle and Peter meet on their journey.
Terry Bradshaw as himself, a retired football player and one of the potential fathers of Kyle and Peter.
Ving Rhames as Rod Hamilton, a retired football player and friend/ex-teammate of Bradshaw.
Harry Shearer as Gene, Helen's new husband.
June Squibb as Mrs. Hunt, Roland Hunt's mother.
Jack McGee as Patrick "Sparkly P" O'Callaghan, a retired police officer in Worcester, Massachusetts and one of the potential fathers of Kyle and Peter who was dead before Kyle and Peter arrived.
Jack McGee also portrays Kevin O'Callaghan, Patrick's twin brother.
Ryan Cartwright as Liam O'Callaghan, one of Patrick's sons.
Ryan Gaul as Sean O'Callaghan, one of Patrick's sons who is not very bright.
Ali Wong as Ali, Dr. Tinkler's nurse.
Retta as Annie, Helen and Gene's wedding planner.
Jessica Gomes as Kaylani Reynolds, Kyle's girlfriend later wife.
Katie Aselton as Sarah O'Callaghan, the daughter of Patrick, niece of Kevin, and sister of Sean and Liam.
Zachary Haven as Ethan, Peter's teenage son who hates him.
Mary Grill as Katherine, Peter's ex-wife and Ethan's mother.
Debra Stipe as Karen Bradshaw, the wife of Terry Bradshaw.
Robert Walker Branchaud and B'nard Lewis as the police officers who direct Kyle and Peter to where Patrick lives.
Andrew Wilson as a quiet-talking hotel desk clerk
Taylor Treadwell as Kelly, the girlfriend of Liam.
Jim France as Father McManus, a priest who presides over Patrick's wake
Brian Huskey as Joel (uncredited)