Diets with higher protein (1.5 g x kg(-1) x d(-1)) and reduced carbohydrates (120 to 200 g/d) appear to enhance weight loss due to a higher loss of body fat and reduced loss of lean body mass. While studies of prolonged use of moderate protein diets are not available, short-term studies report beneficial effects associated with increased satiety, increased thermogenesis, sparing of muscle protein loss, and enhanced glycemic control. Combined impacts of a moderate protein diet are likely derived from lower carbohydrates resulting in lower postprandial increase in blood glucose and lower insulin response, and higher protein providing increased BCAA leucine levels and gluconeogenic substrates. A key element in the diet appears to be the higher intake of BCAA leucine with unique regulatory actions on muscle protein synthesis, modulation of the insulin signal, and sparing of glucose use by stimulation of the glucose-alanine cycle. This review focuses on the contributions of leucine and the BCAA to regulation of muscle protein synthesis and glycemic control.