Orexin, also called hypocretin, is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Orexin exhibits its physiological effects after binding two G-protein-coupled receptors, orexin 1 receptor and orexin 2 receptor. Impairment of the orexin signal, either by deletion of the prepro-orexin or orexin 2 receptor gene or by the ablation of orexin neurons, results in a sleep disorder similar to narcolepsy, suggesting that the orexin system plays an important role in the regulation of sleep/wakefulness. In addition, previous studies have suggested that orexin is involved in energy and fluid homeostasis, emotion regulation, stress responsiveness, and reward. However, growing evidence also suggests that orexin affects the function of peripheral tissues via direct activation of orexin receptors or through activation of autonomic nervous or endocrine systems. In this review, we discuss the physiological roles of orexin not only in the central nervous system but also in the peripheral tissues.