: The World Health Organization estimates that over four million children have been infected with HIV, most via perinatal transmission. The availability of safe and effective antiretroviral therapy (ART) has radically reduced mortality in this population and most that have access to ART are now thriving. However, long-term effects of HIV infection and its therapy have significant impact on aging adolescents and young adults with perinatal HIV infection. Many of the complications of long-term HIV infection seen in adults are also present, although the main impact of long-standing HIV infection and its treatment in children has been on growth and development, including neurodevelopment. A better understanding of the complexities of growing up with perinatal HIV will help prepare low and middle-income countries of the world where ART is now available to successfully manage their aging up populations of adolescents and young adults with perinatal HIV infection.