Severe injury profoundly alters two important hormonal mediators of skeletal muscle. Cortisol production, and the subsequent effect on muscle catabolism, is immediately and persistently elevated. To the contrary, testosterone, a primary anabolic stimulus of skeletal muscle, is considerably suppressed with trauma. The result is a dramatically increased catabolic/anabolic hormonal profile that is further exacerbated by the prolonged inactivity that occurs with severe injury. These factors combine to produce a conspicuous loss of lean body mass throughout hospitalization. Emerging evidence suggests that one approach to ameliorating the loss of skeletal muscle nitrogen is restoration of the anabolic influence. The safe and effective normalization of testosterone concentrations after severe injury attenuates the loss of muscle protein. The retention of lean body mass will positively affect clinical and rehabilitative outcomes.