Human immunodeficiency virus (HIV) infection is strongly associated with ischemic stroke in the young. Data obtained from the Nationwide Inpatient Sample in the United States show an increase in the number of stroke hospitalizations in the HIV-infected population despite an overall decrease in the number of stroke hospitalizations. Few data exist, however, that address the mechanism of HIV-associated stroke. Recent studies have demonstrated that HIV may infect the endothelium and alter cerebrovascular functions. Whether the proposed mechanism alters the stroke risk is undetermined. Epidemiological studies suggest that HIV-related stroke is associated with a risk factor profile that differs from the HIV-negative young stroke population in that HIV-associated strokes are less likely to have hypertension, diabetes, hyperlipidemia and smoking as risk factors. A large population-based study, moreover, suggests an association between antiretroviral therapy and increased cardio- and cerebrovascular risks. Specific antiretroviral agents such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been implicated in the metabolic syndrome, accelerated atherosclerosis and an increased risk for ischemic stroke. In addition to discussing these developments, this paper also discusses the implications of recent data for stroke prevention in HIV-infected patients.