Testosterone-induced nitrogen retention in castrated male animals, eunuchoidal men, pre-pubertal boys and women, and the sex-related differences in the size of the muscles between male and female animals, have been cited as evidence that testosterone has anabolic effects. Recent studies have reported that replacement doses of testosterone in hypogonadal men and supraphysiological doses in eugonadal men increase fat-free mass, muscle size and strength. These effects have provided the rationale for exploring these anabolic applications in sarcopenic states. Although emerging data demonstrate modest gains in fat-free mass in HIV-infected men given replacement doses of testosterone, we do not know whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in patients with wasting disorders.