The emergence of a new metabolic syndrome in patients with HIV infection, termed "HIV-associated dyslipidemic lipodystrophy" (HADL), is characterized by central fat redistribution, severe dyslipidemia, and insulin resistance and predisposes to an increased risk of cardiovascular disease. The factors promoting the development of cardiovascular disease in this condition are not well understood and may involve contributions from antiretroviral drugs and components of the HIV virus, as well as inflammatory cytokines, leading to accelerated lipolysis, dyslipidemia, lipotoxic insulin resistance, and vascular inflammation. In this article, we review HADL in terms of metabolic, molecular, and cytokine derangements leading to cardiovascular disease.