The introduction of highly active antiretroviral therapy has significantly reduced morbidity and mortality in patients infected with the human immunodeficiency virus. Treatment with antiretroviral agents--protease inhibitors in particular--has uncovered a syndrome of abnormal fat redistribution, dyslipidemia, and impaired glucose metabolism, collectively termed lipodystrophy syndrome. The cause of the syndrome seems to be multifactorial; however, its exact mechanisms have yet to be elucidated. Accelerated risk for cardiovascular disease is likely to be a major concern in these patients in the future. At this time, no clinical guidelines are available for the prevention and/or the treatment of lipodystrophy syndrome. The available treatment options range from switching the different antiretroviral drugs and lifestyle modifications to the use of pharmacologic agents to treat patients with dyslipidemia, impaired glucose tolerance and/or diabetes, and changes in body composition. This review emphasizes the clinical features, potential molecular mechanisms, and treatment options for patients infected with human immunodeficiency virus who have lipodystrophy syndrome.