The neuropeptides orexin A and orexin B, produced in hypothalamic neurons, are critical regulators of sleep/wake states. Deficiency of orexin signaling results in narcoleptic phenotype in humans, dogs, and rodents. Recently, accumulating evidence has indicated that the orexin system regulates sleep and wakefulness through interactions with neuronal systems that are closely related with emotion, reward, and energy homeostasis. In this review, we will discuss the current understanding of the physiology of the orexin system especially focusing on its roles in the regulation of sleep/wakefulness states.