The role of body fat in the control of food intake is considered from the point of view that the oxidation of metabolic fuels generates a signal that governs feeding behavior. According to this perspective, the storage and mobilization of fat affect food intake indirectly by altering fuel oxidation. Hyperphagia during the development of obesity is thus treated as an appropriate response to a primary metabolic defect that causes fuels to be stored rather than oxidized. Evidence is presented that changes in insulin level and the activity of carnitine palmitoyltransferase I modulate feeding by altering the partitioning of fatty acids. The possibility that dietary interactions, acting through these mechanisms, may cause overeating of high-fat diets is discussed. It is proposed that the signal for feeding originates in the liver when both fatty acids and glucose are unavailable for oxidation.