AbstractHumans can maintain health on diets differing widely in their macronutrient content, and numerous diet recommendations have been made to maintain health and to help weight control. Net adenosine triphosphate yields during the oxidation of carbohydrate, fat, and protein come to 75%, 90%, and 55%, respectively. However, macronutrient proportions can only be varied within limits, and differences in energy dissipation achievable by macronutrient exchanges are minor. In the National Health and Nutrition Examination Survey III data, stature explains 10% to 16% of the variance in fat‐free mass in adults (the most significant predictor of resting energy expenditure), but <1% of the variance in the percentage of body fat. Thus, differences in resting energy expenditure cannot be expected to have much effect on adiposity. Recommendations designed to facilitate weight control, therefore, should be based on their potential impact on food consumption and energy intake. They should also reflect the fact that the logic for nutrient selection is not the same during weight maintenance and weight reduction. Glycogen levels, along with inherited traits and exercise habits, influence fat oxidation, and, hence, the size that the adipose tissue mass has to reach for fat oxidation to become commensurate with fat intake. Recent increases in the prevalence of obesity could have been brought about by the effect of changes in the food supply and by further declines in physical activity on habitual glycogen levels. Given that biological evolution led to food intake regulating mechanisms that are more powerful in promoting search for food than in seeking to restrain energy intake, it is not surprising that constant availability of desirable foods would lead to a high prevalence of obesity.