The present volume covers all aspects of the topic, from a history of pain through invertebrate model systems to the human genetics of pain and functional imaging. Chapters include the role of ion channels, the opioid system, the immune and sympathetic systems, as well as the mechanisms that transform acute to chronic pain. Migraine and the interplay between sleep and pain are also discussed. New technology in the form of transgenic animals, chemogenetics, optogenetics, and proteomic analyses are providing significant advances in our research and are covered as well. Demystifying pain through an understanding of its fundamental biology, as outlined in this volume, is the most direct route to ameliorating this vast human problem.