Highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of patients with human immunodeficiency virus (HIV). Specific toxicities cited for HAART include elevations in serum levels of total cholesterol and triglycerides, reduction in high-density lipoprotein cholesterol, alterations in the distribution of body fat, increases in insulin resistance, and diabetes, which are major risk factors for cardiovascular disease (CVD). The majority of the studies examining the incidence of CV events demonstrated an increase in CV event rate with HAART in the HIV-infected population. Overall, the CVD risk appears to be greater in the HIV-infected population than in the general population, and the increased CV risk is associated with HAART, particularly with protease inhibitor use. Despite the relative risk (RR) for CVD being significantly high (the hazard ratio for myocardial infarction ranging between 1.3 and 7.1), the absolute risk for CVD remains low, with the CV event rates ranging between one and seven events per 1000 person-years. Although there is general consensus that the benefits of HAART far outweigh toxicity-related risks of the treatment with HAART, prolonged survival among HIV-infected patients will likely support the use of different antiretroviral regimens with potentially less CV toxicity in the future.