Highly active antiretroviral therapy (HAART) has significantly improved the prognosis for many individuals with HIV infection. Consequently, HIV infection has become a chronic and manageable disease. The focus on long-term management of patients with HIV infection has broadened to include comorbid conditions, most notably cardiovascular disease. Patients with HIV infection share many cardiovascular risk factors with the general population, and HIV infection itself may increase cardiovascular risk. Changes in lipid profiles associated with increased cardiovascular risk that have been observed with some HAART regimens have been a cause for concern among clinicians who treat HIV-infected patients. However, the lipid effects of HAART seem to depend on the type and duration of regimens employed. They can be managed effectively according to current guidelines that recommend lifestyle changes (eg, improved diet, increased exercise, smoking cessation) and pharmacologic therapy described in established treatment paradigms for patients on antiretroviral therapy and similar to measures currently used by the general population. A review of the clinical data indicates that the virologic and immunologic benefits of HAART clearly outweigh any metabolic effects observed in some patients over time and that preexisting, established cardiovascular risk factors contribute significantly to the potential development of cardiovascular events. These benefits of antiretroviral therapy have been demonstrated in studies comparing the superior efficacy of continuous vs. intermittent HAART.