Orexins are neuropeptides that are localized in neurons within the lateral hypothalamus and regulate feeding behavior. The lateral hypothalamus plays an important role in not only feeding but also in the central regulation of gut function. Along this line, accumulating evidence has shown that orexins act in the central nervous system to regulate gastrointestinal functions. The purpose of this review is to summarize recent relevant findings on brain orexins and the digestive system, and discuss the pathophysiological roles of these peptides. Centrally administered orexin or endogenously released orexin in the brain potently stimulates gastric acid secretion in rats. The vagal cholinergic pathway is involved in the orexin-induced stimulation of acid secretion. Because of its stimulatory action on feeding, it can be hypothesized that orexin in the brain is a candidate mediator of cephalic phase gastric secretion. In addition, brain orexin may be involved in the development of depression and functional gastrointestinal disorders, which are frequently accompanied by inhibition of gut function, because lack of orexin activity might cause the inhibition of gastric physiological processes and evoke a depressive state. These lines of evidence suggest that orexin in the brain is a potential molecular target for treatment of functional gastrointestinal disorders.