Changes in body composition and metabolism have been a central feature of HIV infection from the outset--initially, as the wasting syndrome and, more recently, as metabolic and body fat redistribution syndromes associated with antiretroviral (ARV) therapy. Here, advances in physiologic and biochemical understanding of these conditions are reviewed. First, the pathophysiology of wasting in HIV-1 infection is discussed, focusing on the failure of nutrients to increase lean tissue ("anabolic block") and the role of hypogonadism. Results of anabolic interventions, including recombinant growth hormone, testosterone, and progressive resistance exercise, are presented. Next, ARV-associated disorders are reviewed, including lipoatrophy and an hypothesized "mitochondrial toxicity." The possibility of establishing pathogenesis in vivo in humans, by direct measurement of mitochondrial DNA synthesis and adipocyte proliferation, is discussed. In summary, important advances have occurred toward the goal of explaining body composition and metabolic abnormalities associated with HIV disease.