The former "Saturday Night Live" cast members star in the new comedic drama as Maggie and Milo -- siblings who reconnect after a ten year estrangement and help sort each others' lives.
Maggie is trying to conceive with her husband Lance (Luke Wilson), until an affair with her scuba instructor makes her question the couple's plans for a family. Milo is a gay struggling actor who decides to confront an old love, played by "Modern Family" star Ty Burrell.
"The Skeleton Twins" was directed by Craig Johnson, marking his sophomore effort after 2009's "True Adolescents." The script was written by Mark Heyman, known for penning "The Wrestler" and "Black Swan" screenplays.
Watch the trailer below to see Wiig and Hader rock out to Starship's 1987 classic single, "Nothing's Going to Stop Us Now."
"The Skeleton Twins" arrives in theaters on Sept. 19.