Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.