Although highly active antiretroviral therapy (HAART) has positively altered the morality rates in HIV-infected children, these drugs have the potential to cause significant morbidity. These drugs cause changes in fat distribution, lipid profiles, glucose, homeostasis, and bone turnover. The direct relationship between duration of drug exposure and increased risk of cardiovascular disease is particularly concerning for HIV-infected infants and children, who likely will have longer cumulative exposure to HAART. It is unclear whether the metabolic effects of decades of exposure would be reversible with cessation of therapy. The benefits of HAART in HIV infection are indisputable, but the impetus to find a cure or design more tolerable therapy is clear. Infarction may replace infection as the major cause of morbidity and mortality from HIV.