Abstract: I argue that the second essay of Nietzsche’s Genealogy of Morality (GM II) provides an account of morally responsible agency, rooted in our susceptibility to the feeling of guilt. Specifically, I argue that GM II’s naturalistic and developmental account of the origins of conscience, bad conscience, and guilt explains why human beings are, in general, appropriate targets of the moral reactive attitudes. I motivate this reading by appealing to P.F. Strawson’s naturalistic analysis of responsibility in “Freedom and Resentment,” showing that GM II likewise analyzes responsibility in terms of the practice of holding others and oneself responsible. This practice is constituted by what Nietzsche calls the “reactive affects,” and I argue that these attitudes not only legitimize blame, but also trust (“permitted promising”), in connection to Nietzsche’s positive ideal of responsibility, the “sovereign individual.”