Whether the atherogenic metabolic side effects of highly active antiretroviral therapy (HAART) (lipid disorders and glucose intolerance/diabetes) will translate, in the long term, into an increased incidence of cardiovascular events that would offset the survival benefits of this type of therapy is a matter of intense concern. This concern has been substantiated by a series of case reports of HIV-infected patients who had experienced unexplained cardiovascular disease. However, in the absence of prospective, large cohort studies, the answer to this question at present remains elusive. Indirect evidence, from retrospective cohort analyses and non-invasive imaging of peripheral arteries, indicates that HIV-infected persons are at higher risk for atherosclerosis than HIV-negative individuals. However, this risk does not appear to be attributable to HAART. Pending the availability of further data, a global assessment of the risk for heart disease should be performed in all HAART-treated HIV-infected patients, taking into account age and the presence of major risk factors. There is so far no evidence, from a cardiovascular standpoint, to limit administration of HAART. However, interventions on modifiable risk factors, including smoking cessation, are strongly recommended, particularly in high-risk patients.