Insulin is now well established as an adiposity signal that acts in the brain to influence energy homeostasis. It is secreted in direct proportion to adiposity; it enters the brain from the blood, and it interacts with neurons in the ventral hypothalamus. Experimental manipulation of brain insulin causes predictable changes of food intake and body weight. Because insulin shares many properties with other adiposity signals, especially leptin, in this regard, it is important to recognize the similarities and differences in the signal each conveys to the brain in order to design effective therapeutic approaches to treat pathologies of eating and body weight.