This paper compares the efficacy of two widely used weight-loss diets differing in macronutrient composition - a low-carbohydrate diet versus a low-fat diet. Although "a calorie is a calorie" under the controlled conditions of a metabolic unit (i.e., only the level of calorie intake matters and not the source of calories), we conclude that these interrelationships are far more complex in the free-living situation. The different diet-related factors that condition energy balance, including total energy intake, satiety and hunger sensory triggers, and palatability, must be considered when assessing the efficacy of weight-reducing diets of different macronutrient composition.