HIV-associated lipodystrophy characterized by body composition changes and associated metabolic abnormalities, including dyslipidemia and insulin resistance, is a major challenge in the treatment of HIV infection. Growth hormone-releasing factor (GRF) analogs with greater stability than the natural hormone can induce growth hormone secretion in a physiological manner, and appear to be promising candidate therapies for these conditions. The most promising GRF agonist in development is tesamorelin (EMD Serono/Theratechnologies), which has exhibited efficacy for the treatment of excess visceral adipose tissue in patients with HIV infection in two recent phase III, randomized, placebo-controlled clinical trials. Additional long-term outcome trials are required to determine the long-term safety of tesamorelin and to evaluate whether this agent, or other GRF agonists, could reduce the cardiovascular risk associated with lipodystrophy-related metabolic complications and help to maintain a more normal distribution of body fat.