Controlled experiments on the relative efficiency of carbohydrate, fat and protein in weight reduction diets indicate that obese people lose more weight when most of the calories are derived from fat. These findings are explained by a concept of obesity as due to an impairment in the oxidative pathway of pyruvic acid. Recent advances in the biochemistry of pyruvic acid are reviewed and an attempt is made to identify the precise point at which the metabolic defect occurs. Implications in treatment are mentioned.