Results from several studies have suggested that people with HIV have an increased risk of cardiovascular disease, especially coronary heart disease, compared with people not infected with HIV. People living with HIV have an increased prevalence of traditional cardiovascular disease risk factors, and HIV-specific mechanisms such as immune activation. Although older, more metabolically harmful antiretroviral regimens probably contributed to the risk of cardiovascular disease, new data suggest that early and continuous use of modern regimens, which might have fewer metabolic effects, minimizes the risk of myocardial infarction by maintaining viral suppression and decreasing immune activation. Even with antiretroviral therapy, however, immune activation persists in people with HIV and could contribute to accelerated atherosclerosis, especially of coronary lesions that are susceptible to rupture. Therefore, treatments that safely reduce inflammation in people with HIV could provide additional cardiovascular protection alongside treatment of both traditional and non-traditional risk factors.