The hypothalamus integrates various hormonal and neuronal signals to regulate appetite and metabolism and thereby serves a homeostatic purpose in the regulation of body weight. Additional neural circuits that are superimposed on this system have the potential to override the homeostatic signals, resulting in either gluttony or anorexia at the extremes. Midbrain dopamine neurons have long been implicated in mediating reward behavior and the motivational aspects of feeding behavior. Recent results reveal that hormones implicated in regulating the homeostatic system also impinge directly on dopamine neurons; for example, leptin and insulin directly inhibit dopamine neurons, whereas ghrelin activates them. Here, I discuss the predictions and implications of these new findings as they relate to dopamine signaling and the physiology of appetite control.