Food intake and energy expenditure are controlled by complex, redundant, and distributed neural systems that reflect the fundamental biological importance of adequate nutrient supply and energy balance. Much progress has been made in identifying the various hormonal and neural mechanisms by which the brain informs itself about availability of ingested and stored nutrients and, in turn, generates behavioral, autonomic, and endocrine output. While hypothalamus and caudal brainstem play crucial roles in this homeostatic function, areas in the cortex and limbic system are important for processing information regarding prior experience with food, reward, and emotion, as well as social and environmental context. Most vertebrates can store a considerable amount of energy as fat for later use, and this ability has now become one of the major health risks for many human populations. The predisposition to develop obesity can theoretically result from any pathological malfunction or lack of adaptation to changing environments of this highly complex system.