HIV-infected individuals represent a unique and increasing subset of atherosclerosis. With the advent of antiretroviral therapy, HIV-infected individuals now have much improved survival and are faced with health issues related to aging, including cardiovascular disease. Individuals with HIV have higher rates of coronary events compared to controls even in the setting of treated and suppressed disease and a growing body of literature suggests that they are at increased risk for myocardial infarction, atherosclerosis, and sudden cardiac death. Many facets of atherosclerosis differ in HIV-infected individuals compared to uninfected individuals with atherosclerosis. HIV-infected patients with acute coronary syndromes are younger and more likely to be males and smokers, with low high density lipoprotein-cholesterol (HDL-C), compared to other acute coronary syndrome patients. With respect to pathophysiology, viral replication, antiretroviral drugs all contribute to atherosclerosis.