"The Sisters Brothers" is a novel by author Patrick deWitt. The story follows Eli and Charlie Sisters. The two men are brothers, who are also contract killers that work for the commodore. The Sisters Brothers set out for San Francisco, California to complete their next job for the commodore, which is to find and kill Hermann Kermit Warm. According to Charlie Sisters, the commodore wants him to take the lead on this particular assignment so the brothers don't encounter any of the problems they did on their previous job assignment.

The two brothers set out on their horses, Nimble and Tub, on the two-week journey to San Francisco. Even with Charlie acting as the lead for the job, the two brothers encounter obstacle after obstacle along the way. One of the biggest obstacles is Charlie Sisters himself. Charlie frequents saloons and typically ends his nights in a drunken stupor. Waking up with a hangover almost every morning, Eli Sisters heads to the chemist to buy some morphine to help Charlie feel better so they can continue on their journey.

Each person the brothers come into with and the experiences they have along the way transform and shape them as human beings. By the end of the novel, they collaborate with the man they are supposed to kill and kill the man that hired them. Both brothers change forever, turning in their careers as contract killers for a more traditional and quieter life.