In a restrictive food environment, the homeostatic control system regulates body weight and adiposity with remarkable precision. However, this regulation appears to break down in many genetically predisposed individuals under conditions prevailing in the modern era characterized by a sedentary lifestyle and easy availability of large portions of palatable and calorically dense food. The nervous system is the main interface by which food-related environmental factors influence the regulatory process. Thus, focusing on the neural systems located in the telencephalon dealing with environmental factors, and on their connections with the homeostatic regulatory system distributed mainly in the hypothalamus and brainstem, should result in new drug targets and behavioral strategies for prevention and therapy. The structures providing this interface with the environment are involved in the initiation, procurement, and appetitive phases of ingestive behavior and associative learning before, during, and after the consummatory phase. It is thought that learned and unlearned representations of foods and food cues in the orbitofrontal and other cortical areas are filtered for affective/emotional value in the amygdala and for motivational salience in the nucleus accumbens/ventral striatum to initiate goal-directed motor programs. Internal state signals generated by the metabolic sensing mechanisms in the hypothalamus interact with each of these corticolimbic structures through reciprocal connections. While many projections from the hypothalamus contain the various "feeding peptides," the neurochemistry of projections to the hypothalamus has not been well characterized.