Recent progress in the field of energy homeostasis was triggered by the discovery of adipocyte hormone leptin and revealed a complex regulatory neuroendocrine network. A late addition is the novel stomach hormone ghrelin, which is an endogenous agonist at the growth hormone secretagogne receptor and is the motilin-related family of regulatory peptides. In addition to its ability to stimulate GH secretion and gastric motility, ghrelin stimulates appetite and induces a positive energy balance leading to body weight gain. Leptin and ghrelin are complementary, yet antagonistic, signals reflecting acute and chronic changes in energy balance, the effects of which are mediated by hypothalamic neuropeptides such as neuropeptide Y and agouti-related peptide. Endocrine and vagal afferent pathways are involved in these actions of ghrelin and leptin. Ghrelin is a novel neuroendocrine signal possessing a wide spectrum of biological activities that illustrates the importance of the stomach in providing input into the brain. Defective ghrelin signaling from the stomach could contribute to abnormalities in energy balance, growth, and associated gastrointestinal and neuroendocrine functions.