It is 1851, and Charlie and Eli Sisters ( Joaquin Phoenix and John C. Reilly ) are both brothers and assassins, boys grown to men in a savage and hostile world. They have blood on their hands: that of criminals, that of innocents...and they know no state of existence other than being gunmen. The older of the two, introspective Eli ( Reilly ) rides hard with his younger sibling yet dares to dream of a normal life. The younger of the two, hard-drinking Charlie ( Phoenix ) has taken charge with gusto as lead man on the duo's assignments. Each increasingly questions, and quibbles with, the other's methods. The Sisters brothers find themselves on a journey through the Northwest, bringing them to the mountains of Oregon, a dangerous brothel in the small town of Mayfield, and eventually, the Gold Rush land of California - a journey that will test the deadly family ties that bind. But, can it also be the path to rediscovering what remains of their humanity? THE SIS