Evidence is accumulating that diets with reduced carbohydrates and increased levels of high quality protein are effective for weight loss. These diets appear to provide a metabolic advantage during restricted energy intake that targets increased loss of body fat while reducing loss of lean tissue and stabilizing regulations of blood glucose. We have proposed that the branched-chain amino acid leucine is a key to the metabolic advantage of a higher protein diet because of its unique roles in regulation of muscle protein synthesis, insulin signaling and glucose re-cycling via alanine. These metabolic actions of leucine require plasma and intracellular concentrations to increase above minimum levels maintained by current dietary guidelines and dietary practices in the U.S. Initial findings support use of dietary at levels above 1.5 g/kg . d during weight loss. Further, our research suggests that increased use of high quality protein at breakfast maybe important for the metabolic advantage of a higher protein diet.