Human behavior emerges from a complex dynamic interaction between graded and context-sensitive neural processes, the biomechanics of our bodies, and the vicissitudes of our environments. These coupled processes bear little resemblance to the iterated application of simple symbolic rules. Still, there are circumstances under which our behavior appears to be guided by explicit mental rules. A prototypical case is when succinct verbal instructions are communicated and are promptly followed by another. How does the brain support such rule-guided behavior? How are explicit rules represented in the brain? How are rule representations shaped by experience? What neural processes form the foundation of our ability to systematically represent and apply rules from the vast range of possible rules? This article reviews a line of research that has sought a computational cognitive neuroscience account of rule-guided behavior in terms of the functioning of the prefrontal cortex, the basal ganglia, and related brain systems.