Our knowledge of the physiological systems controlling energy homeostasis has increased dramatically over the last decade. The roles of peripheral signals from adipose tissue, pancreas, and the gastrointestinal tract reflecting short- and long-term nutritional status are now being described. Such signals influence central circuits in the hypothalamus, brain stem, and limbic system to modulate neuropeptide release and hence food intake and energy expenditure. This review discusses the peripheral hormones and central neuronal pathways that contribute to control of appetite.