Orexin-A and -B are initially identified as endogenous ligands for an orphan G protein coupled receptor. Since the discovery of orexins, investigations of their functions have been guided by their distribution in the lateral hypothalamic area, which has been implicated in feeding behavior. In fact, when administered intracerebroventricularly in early light phase, orexin-A stimulated food consumption. Orexin mRNA is up-regulated by fasting, suggesting their expression is regulated by animal's nutritional status. The orexin neurons project widely in the brain, and thus the physiological role of orexins is likely to be complex. Orexin neurons in the lateral hypothalamic area was shown to receive terminal appositions from NPY-, AgRP-, and a-MSH-IR fibers. The innervation of orexin neurons by peptidergic fibers corresponding to leptin-responsive cell types that reside in the arcuate nucleus may have a role in linking peripheral metabolic cues to autonomic regulatory sites and the cerebral cortical mantle, providing a neuroanatomic basis for regulation of feeding behavior. The wide distribution of orexin-immunoreactive fibers in the brain has also suggested their additional roles. Actually, orexins have been reported to have roles in regulating drinking behavior, neuroendocrine function and the sleep-wake cycle.