Tremendous success in the prevention and treatment of pediatric HIV in high-resource countries has changed the face of the epidemic. A perinatally HIV-infected child now faces a chronic disease rather than a progressive, fatal one. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. These include maintaining adherence to long-term, likely life-long therapy; selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations and the lack of pharmacokinetic and safety data in children; and overcoming extensive drug resistance in multi-drug-experienced children. Pediatric HIV care now focuses on morbidity related to long-term HIV infection and its treatment. Survival into adulthood of perinatally HIV-infected youth in high-resource countries encourages expansion of pediatric treatment programs in low-resource countries, where most HIV-infected children live, and provides important lessons about how the epidemic changes with increasing access to antiretroviral therapy for children.