Muscle mass is critical for athletic performance and, perhaps more importantly for most, health and survival. The metabolic basis for a change in muscle mass is an increase in net muscle protein balance (termed NBAL). NBAL is the difference between MPS (muscle protein synthesis) and MPB (muscle protein breakdown). Thus an increase in MPS and/or a decrease in MPB are necessary for NBAL to increase, leading to accretion of muscle proteins. In particular, accretion of myofibrillar proteins is necessary. NBAL responds to exercise, feeding and other factors. In healthy, weight-stable adults, muscle mass remains constant because periods of positive balance following feeding are countered by periods of negative balance during fasting. A combination of resistance exercise and nutrition is a potent anabolic stimulus through stimulation of MPS from amino acids and attenuation of MPB by carbohydrates. Increased muscle mass results from the accumulation of small amounts of protein in response to each bout of exercise combined with nutrient intake. The magnitude of the response may be influenced by factors other than just the amount of a nutrient ingested. Timing of ingestion, co-ingestion of nutrients and the type of protein may all influence protein accretion. Testosterone is a potent anabolic stimulus primarily through improvement in re-utilization of amino acids from MPB. There is a general lack of efficacy in studies assessing the potential for growth hormone, androstenedione and dehydroepiandrostenedione to increase muscle mass. Creatine supplementation is clearly an effective means to increase muscle mass, especially in combination with resistance exercise, however the mechanisms remain unclear. Results from acute metabolic studies provide useful information for estimation of the efficacy of anabolic agents.