Hypocretins (orexins) are recently discovered excitatory neuropeptides produced only in the posterolateral hypothalamus. These neurotransmitters play a key role in sleep-waking regulation. In patients with narcolepsy and cataplexy, hypocretin neurotransmission is deficient, as demonstrated by low or undetectable levels of hypocretin-1 in the cerebrospinal fluid. The etiology of this deficiency is not clear. In most patients with other hypersomnolent syndromes or sleep-waking disturbances, hypocretin neurotransmission is normal. Other functions of the hypocretins include the regulation of food intake and of neuroendocrine mechanisms.