As new therapies for HIV infection have been developed, some of the clinical focus related to AIDS and HIV infection has shifted from acute care, to more chronic issues. Some of these new clinical issues seem related to the HIV infection itself, while others seem to be side effects of therapeutic efforts. Metabolic abnormalities, such as dyslipidemia, insulin resistance, and lipodystrophy (LD) have been observed. The clinical importance of these is demonstrated by the increased prevalence of cardiovascular disease and diabetes in HIV infected persons. LD is a general term used to describe varying degrees of fat redistribution, including lipoatrophy and lipohypertrophy, in different body regions. Though LD was observed in persons with HIV infection before highly active treatment regimens were developed, the prevalence of LD has seemingly increased drastically with the widespread use of more active therapies. It has been postulated that protease inhibitors (PI), especially, are linked to the development of LD. This review will assess the epidemiologic information related to HIV-associated LD, and related metabolic syndromes. In addition, potential mechanisms accounting for these syndromes will be reviewed. In general, the available data do not define a single, definable etiology or mechanism explaining these clinical conditions, but suggest that these conditions are caused by a complex interaction potentially involving such things as the side effects of medications, alteration of immune function, and individual subject characteristics, such as body weight and baseline lipid level.