Cardiovascular disease (CVD) is the leading cause of non-HIV-related death in HIV-infected persons. The risk of CVD in HIV-infected persons appears to reflect the contribution of a number of factors, including non-HIV-related (traditional) cardiovascular risk factors, chronic inflammation associated with HIV infection, and metabolic adverse effects of antiretroviral therapy. Traditional CVD risk factors, however, are the major determinants of risk in HIV-infected patients and this population carries a high burden of such factors. HIV infection may also be an independent risk factor for CVD, but there is not yet sufficient evidence to consider HIV infection itself a coronary heart disease risk equivalent (eg, in the same manner as diabetes) or to change calculation of risk in the HIV-infected population. In the absence of specific randomized trials in the HIV-infected population, HIV-infected persons should be treated for cardiovascular risk factors according to current national guidelines for reducing risk, including those for aspirin use and for treatment of dyslipidemia, hypertension, and metabolic syndrome. This article summarizes a presentation by Wendy S. Post, MD, at the 14th Annual Clinical Conference for the Ryan White HIV/AIDS Program held in Tampa, Florida, in June 2011. Dr Kerunne Ketlogetswe provided additional editing. The Clinical Conference is sponsored by the IAS-USA under the Health Resources and Services Administration (HRSA) contract number HHSH250200900010C.