Among the many events in The Sisters Brothers, two stand out as being particularly significant in connecting with its central themes. The first is the burning and subsequent amputation of Charlie's hand. Charlie's hand is burned by the caustic gold-finding formula, which represents the toxic properties of capitalism and greed, an important theme in the story. This is the hand Charlie uses for shooting, and without it, he is helpless and emasculated, becoming dependent on Eli, the brother he has always treated as a junior partner in crime, to care for him. This means that Charlie's loss of his hand is also related to the theme of masculine violence which runs through the book.
The second event is Eli's murder of the brothers' mysterious employer, the Commodore. The Commodore hired them to kill the gold prospector Hermann Kermit Warm, who was in fact killed by diving into a river full of his own toxic gold-finding formula (another illustration of the deadliness of greed). Eli is tired of killing and wants to leave the life of a hired assassin behind him. However, in order to do so, he has to kill the man who hired him as an assassin. This incident, which is characteristic of the irony in the novel, emphasizes the themes of the value (or cheapness) of human life and the perils of engaging in crime.