Greater average weight losses (2.5 kg over 12 weeks) have been reported for low-carbohydrate diets (<90 g/day) compared with traditional low-fat (<25% of energy), hypocaloric diets, implying a 233 kcal/day greater energy deficit. It has therefore been suggested that a low-carbohydrate diet may provide a metabolic advantage (an increase in energy expenditure), resulting in a positive effect on weight loss and maintenance. However, a review of studies in which 24-hour energy expenditure was measured did not provide evidence to support a metabolic advantage of low-carbohydrate diets and showed little evidence of a metabolic advantage of high-protein (>25% of energy) diets. Nonetheless, diets high in protein, but either low or modest in carbohydrate, have resulted in greater weight losses than traditional low-fat diets. We speculate that it is the protein, and not carbohydrate, content that is important in promoting short-term weight loss and that this effect is likely due to increased satiety caused by increased dietary protein. It has been suggested that the increased satiety might help persons to be more compliant with a hypocaloric diet and achieve greater weight loss. The current evidence, combined with the need to meet all nutrient requirements, suggests that hypocaloric weight-loss diets should be moderate in carbohydrate (35% to 50% of energy), moderate in fat (25% to 35% of energy), and protein should contribute 25% to 30% of energy intake. More studies of the efficacy of weight-loss and weight-maintenance diets that address protein content are needed. In addition, controlled studies of total energy expenditure or physical activity measured under free-living conditions that directly compare high-protein diets with those containing low and moderate carbohydrate content should also be performed.