Impairment of orexin/hypocretin signaling causes narcolepsy-cataplexy in animals and humans. Most human narcolepsy-cataplexy cases are associated with orexin/hypocretin ligand deficiency, which can be detected clinically using cerebrospinal orexin/hypocretin measures and may lead to future treatments with orexin/hypocretin replacement therapy. In The Orexin/Hypocretin System: Physiology and Pathophysiology, leading researchers and clinicians review these exciting developments to set the stage for further research on the loss of orexin/hypocretin neurons in humans, regulation of sleep and wakefulness by the orexin/hypocretin system, and the role of the orexin/hypocretin system in many other physiological processes, including feeding, autonomic regulation, and neuroendocrine regulation. Topics of interest include an assessment of the functions and the physiology of orexin/hypocretin, its pathophysiology in human narcolepsy-cataplexy, and possible pharmacological treatments. The authors also introduce several experimental methods for orexin/hypocretin research, and, using multidisciplinary approaches, explain their uses and limitations. Authoritative and state-of-the-art, The Orexin/Hypocretin System: Physiology and Pathophysiology will aid scientists in the search for novel bioactive peptides and their receptors, as well as novel physiological insights and opportunities for the clinical treatment of not only narcolepsy, but also a broad range of diseases associated with endocrine, feeding, and body weight regulation.