The Sisters Brothers is a period Western by author Patrick DeWitt that follows brothers Eli and Charlie Sisters, two assassins for hire, through a series of misadventures as they track down a target, Hermann Warm, to eliminate.

At one point, Eli has a strange dream where he witnesses a young girl who is standing with a dog chewing on its own detached leg. The girl infers in a dialogue with Eli that he is a "protected man," although she doesn't refer to him outright. Upon closer inspection of the dog, Eli can see that it is dead from poisoning.

Because Eli is a "protected man," he is later able to save Charlie (who is not "protected") from being poisoned by the little girl. The dog is meant to be a prophetic parallel to Charlie, who loses his shooting hand. Yet time and again throughout the story, we see Eli come out of various debacles unscathed, whether it's Mister Mayfield's bookkeeper saving him from getting murdered by trappers or being the sole individual who emerges from the California hinterlands in one piece after escaping the effects of Warm's deadly formula.

The story makes allusions to the presence of "Fates" that determine man's destiny, the girl in the dream being a prime example. This presents an interesting paradox: feminine figures are eliciting control in a world typically dominated by men. This is externalized by making the bookkeeper savior a woman. It's inferred that her motives are to save Eli because he is willing to eschew the sins of killing, greed and debauchery that generally accompany his profession in exchange for becoming a "real man."

Eli is deemed worthy of being "protected," or saved, in the physical world, but he is being rewarded by a spiritual dimension that has decided his change of heart warrants a second chance. Charlie, however, still deserves to be punished for remaining steadfast to his greedy, murdering ways. The story ultimately promotes the idea of redemption, even for the worst of sins, as long as there is repentance.