Metabolic complications and altered fat distribution associated with HIV infection and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). The high prevalence of multiple cardiovascular risk factors in a significant number of HIV patients is a cause for concern in both patients and physicians. Non-invasive strategies to measure subclinical CAD have been inconclusive. Long-term studies are underway to determine cardiac event rates, intervention strategies and consequences for the clinical management of HIV disease. In the present paper, we summarize the most prevalent risk factors in individuals with HIV infection receiving highly active antiretroviral therapy by focusing on the clinical implications of metabolic abnormalities and HIV-related lipodystrophy on CAD.