Emphasis has been placed on the understanding of the regulation of food intake in the hope of aiding the battle against obesity and of helping to ameliorate the anorexia of cancer and eating disorders. Available data suggest that the regulatory system is multifaceted and complex. This review focuses on current research on the regulation of appetite and satiety by carbohydrates, fats, and proteins as well as by artificial sweeteners. Some methodological problems and potential mechanisms of action at the biochemical level are discussed. Evidence suggests that organisms are more successful in defending against calorie dilution than in adjusting to increases in calories. The implications of that defense relative to the use of ersatz nutrients are explored.