In 1906 Sir Charles Sherrington published The Integrative Action of the Nervous System, which was a collection of ten lectures delivered two years before at Yale University in the United States. In this monograph Sherrington summarized two decades of painstaking experimental observations and his incisive interpretation of them. It settled the then-current debate between the “Reticular Theory” versus “Neuron Doctrine” ideas about the fundamental nature of the nervous system in mammals in favor of the latter, and it changed forever the way in which subsequent generations have viewed the organization of the central nervous system. Sherrington's magnum opus contains basic concepts and even terminology that are now second nature to every student of the subject. This brief article reviews the historical context in which the book was written, summarizes its content, and considers its impact on Neurology and Neuroscience.