Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk factors are often more common among individuals with HIV infection, and traditional prevention strategies remain important. Recent data have revealed that untreated HIV infection itself amplifies additional pro-atherogenic mechanisms related to immune activation, inflammation, coagulation, and lipoprotein particle changes (e.g. high-density lipoprotein particles). Some of these mechanisms are attenuated, though incompletely, with antiretroviral therapy (ART)-related suppression of HIV replication. Exposure to ART is also associated with variable toxicity that may simultaneously decrease (via viral suppression) and increase CVD risk. Ultimately, additional adjunctive treatment will be needed to mitigate premature CVD risk among contemporary HIV-infected patients with access to ART.