The neuropeptides orexin A and B (hypocretin 1 and 2) are produced by one group of neurons located in the lateral hypothalamic area. These neurons receive a variety of signals related to environmental, physiological and emotional stimuli. In turn, they send axons to numerous brain regions implicated in the regulation of the sleep-wake cycle, thereby increasing arousal levels and maintaining wakefulness. Dysregulation or loss of orexin signaling has been linked to a number of pathological conditions. In this review, we present an overview of the current understanding of orexin function, focusing on evidence for the involvement of orexin in sleep disorders and neurodegenerative diseases.