Increased intake of energy dense foods and decreased physical activity are thought to be the major factors responsible for the current obesity epidemic and understanding the biological mechanisms controlling the underlying metabolic processes and behaviors will lead to better strategies for therapy. Ingestive behavior is controlled by a complex interplay between signals conveying availability of 1) potentially ingestible food in the environment, 2) digestible food in the alimentary canal, 3) circulating fuels, and 4) stored fuels in adipose tissue and liver. Each of these four classes of signals interact with specific sensors and neural circuits whose integrated output determines when food intake is initiated and when it is stopped. Because the final common path responsible for oromotor control is contained within complex neural pattern generators within the brainstem and is intimately linked to sensory information from the alimentary canal, at least part of the integration between the four classes of signals is thought to take place at the level of the caudal brainstem. I will present anatomical and functional evidence for the rich supply of food-related information from the alimentary canal and its associated organs delivered to the caudal brainstem through vagal afferents. Modulation of these intrinsic medullary circuits controlling satiation and meal-termination by descending peptidergic projections from the hypothalamus and cortico-limbic systems that carry longer-term nutritional information as well as cognitive, reward, and emotional information will be highlighted. Finally, the potential role of gut-brain communication in bariatric surgery-induced weight loss and improvement of the diabetic state will be briefly evaluated. NIDDK 47348 and DK 071082.