In resourced settings with access to highly active antiretroviral therapy, perinatally acquired HIV-1 infection has become a chronic disease of childhood with increasing numbers of adolescents surviving to adulthood and transitioning from pediatric to adult services. Advances in antiretroviral therapy, reductions in side effects, new classes and new drugs within existing antiretroviral classes offer enormous benefits, although issues around adherence during adolescence persist. The longer term impact of exposure to HIV and antiretroviral therapy throughout childhood are becoming apparent, with growing concern over neurocognitive, cardiovascular, renal and bone health. Careful follow-up of this early perinatal cohort as they enter adulthood will inform the future management of the growing numbers of adolescents surviving worldwide as access to therapy increases.