Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, and other dissociated manifestations of rapid eye movement sleep. The major pathophysiology of human narcolepsy has recently been revealed by the extension of discoveries of narcolepsy genes in animal models. This directly led to the development of new diagnostic tests. The disease is currently treated with amphetamine-like compounds and modafinil for excessive daytime sleepiness and anticataplectics for cataplexy. Clinical, pharmacologic, pathophysiologic aspects of narcolepsy and future directions are discussed.