This chapter provides an overview of the mechanisms involved in the regulation of food intake and the various responses in the gastrointestinal (GI) tract, pancreas, and liver to the ingestion of a meal. The coordination of these processes is essential for the regulation of food intake, the digestion and absorption of nutrients in the food, the distribution, storage, and release of nutrients to meet demand, and the elimination of wastes. Three principal control mechanisms regulate GI function: endocrine, paracrine, and neural. Humoral factors are also involved in the regulation of food intake. The colonic phase is important for the further reabsorption of water and ions and for the storage and elimination of waste products. The regulation of storage and release of nutrients allow for the continuous provision of metabolic fuel for all of the tissues of the body despite the fact the intake of meals are discontinuous.