Much of our behavior is guided by rules, or prescribed guides for action. In this review, I consider the current state of knowledge of how rules are learned, stored in the brain, and retrieved and used as the need arises. The focus is primarily on studies in humans, but the review is informed by relevant studies in nonhuman primates. Ventrolateral prefrontal cortex (VLPFC) has been implicated in rule learning, retrieval from long-term memory, and on-line maintenance during task preparation. Interactions between VLPFC and temporal cortex are required for rule retrieval in nonhuman primates, and brain imaging findings in humans suggest that rule knowledge is stored in the posterior middle temporal gyrus. Dorsolateral PFC appears to be more closely related to rule-based response selection than to rule retrieval. An important task for the future is to explain how PFC, basal ganglia, and temporal, parietal, and motor cortices interact to produce rule-guided behavior.