The Integrative Action of the Nervous System by the British physiologist Charles Sherrington was published 100 years ago. Its goal was to explain how the nervous system welds a collection of disparate body parts and organs into a unified individual. Sherrington postulated that the reflex is the simplest unit of nervous integration. He introduced the concept of the synapse as the site where elementary reflexes interact to enable more complex and unified behavior and argued that a synaptic nervous system facilitated the evolution of the cerebrum and cerebellum. The concept of the synapse as a physiological entity provided a theoretical schema into which the richly varied phenomenology of nineteenth century reflex physiology could be assimilated. Sherrington's book also provided the conceptual framework for a century of research into the mechanisms of synaptic transmission and the neuronal discharges associated with perception and action.