Based on a novel of the same name by Patrick deWitt, tells the story of the brothers Eli (John C. Reilly) and Charlie (Joaquin Phoenix) Sisters, hitmen in the old West. As the movie progresses, we learn about the history of their family (a very abusive, alcoholic father), who they work for, where they're going, who they're going to kill, etc. And that they're very, very good at what they do.
I've seen reference to this being partly a "comedy." It's got a few laughs (most of them dark), but it's certainly not what the movie is primarily about and I think it's a poor choice to apply the term to this movie.
The movie has a lot of action - and pretty much all of it happens off screen. "The point," the director is telling us, "is that this is about the people." If you're looking for a Western with gunfights, look elsewhere: this is a character study. I found it a surprisingly good one: it's very well acted, and pretty much never went where I expected - without ever getting derailed. The ending in particular was absolutely not what I expected: I'm still a bit surprised, and yet it was strangely satisfying.
I'm not much of a fan of Westerns. But when the acting is this good, and the story is this well written and unexpected ... highly recommended.