Craig Johnson’s ‘The Skeleton Twins’ makes its irreverent and offbeat tone obvious early on – thanks to an opening sequences that centers on a haggard Bill Hader penning a suicide note that begins with impersonal (and darkly amusing) salutation, “To Whom It May Concern.” Hader’s Milo is clearly going through something, but it’s still shocking when he dips into a full bath and blood begins to flow, just off-screen and from the direction of his wrists.

An entire country away, Milo’s estranged twin sister, Maggie (Kristen Wiig), is attempting the same act, though she is standing in her bathroom with a fistful of pills hovering beside her mouth. She’s interrupted by a call from the hospital where Milo has just been admitted – and thus the so-called Skeleton Twins (sadly, their last name is not Skeleton, but the nickname is explained) have to do the thing they fear most. They have to live.

Despite the apparent mystery of why both Maggie and Milo tried to kill themselves, Johnson doesn’t focus on those revelations, instead letting them naturally unfold over time. ‘The Skeleton Twins’ is primarily concerned with following the fits and starts of the twins’ clearly fraught relationship, a story it tells with both big drama and more than a few laughs. After Milo’s attempt, Maggie brings him back to their hometown in upstate New York; removing him from his Los Angeles environment for some much needed rest and relaxation. Maggie and Milo haven’t seen each other in nearly a decade, and their first few interactions are peppered with both natural concern (from Maggie) and the stilted sharing of important information (from both of them), like introducing Milo to Lance (Luke Wilson), her “golden retriever” of a husband.

While everyone knows about Milo’s attempt, Maggie keeps mum on hers, and the lingering secret casts a bit of a shadow over their conversations – especially when Maggie is trying to tell Milo what to do. Maggie has been filling her free time with a seemingly never-ending string of enrichment classes, from salsa dancing to scuba diving, and while Lance takes great pride in the apparent can-do spirit of his wife, she has other reasons for her education, and none of them are very good.

Johnson’s somewhat simple story (co-written with Mark Heyman) is consistently elevated by the spirit in which it is told and by two excellent, game-changing performances from its leads. Hader is nothing short of transcendent in his role, playing both bitterness and sensitivity with serious skill, and his work as Milo is a major step forward in his career, the kind the proves that even a funny guy (he’s Stefon, come on!) can handle meaty roles like this. Wiig is solid, too, and she captures the kind of darkness we rarely see from her performances with ease. It doesn’t hurt that both Maggie and Milo are characters that are easy to care about – flaws and all – and Johnson and Heyman’s script make them feel realistic, well-rounded, and relatable, with Hader and Wiig simply driving that point home (over and over, in scene after scene).

But Hader and Wiig, for all their characters’ issues and problems and darkness, are also magical together, and the comedic chemistry that they’ve exhibited so handily in the past here translates to something very special: they are completely believable as twins.

‘The Skeleton Twins’ may sound dark and dreary, but it’s also brisk and entertaining and outfitted with some big laughs. Hader and Wiig clearly have fun together, and when their Maggie and Milo get goofy in various situations, ranging from a laughing gas-fueled giggle fit to a showstopper of a lip-sync to Starship’s “Nothing’s Gonna Stop Us Now,” ‘The Skeleton Twins’ is almost painfully funny. But the film is also appropriately painful, and Johnson’s depiction of mental instability and suicidal tendencies is sensitive and gracefully presented, with two star turns to mark it as a true breakout.

'The Skeleton Twins' premiered at the 2014 Sundance Film Festival.