The behaviors involved in complex human tool use cut across boundaries traditionally drawn between social, cognitive, perceptual and motor processes. Longstanding neuropsychological evidence suggests a distinction between brain systems responsible for representing: (1) semantic knowledge about familiar tools and their uses, and (2) the acquired skills necessary for performing these actions. Contemporary findings in functional neuroimaging support and refine this distinction by revealing the distributed neural systems that support these processes and the conditions under which they interact. Together, these findings indicate that behaviors associated with complex tool use arise from functionally specialized networks involving temporal, parietal and frontal areas within the left cerebral hemisphere.