There are ~1 million people in the United States living with HIV/AIDS, and >50,000 new infections occur each year. With an estimated 13% of all new infections occurring among young people aged 13 to 24 years and an increasing number of perinatally infected youth surviving to adulthood, there is now an increasing need to transition both perinatally and behaviorally infected youth to the adult health care setting. Recently, pediatric providers and professional societies have prioritized the development of transition programs for adolescents with chronic disease to address the many challenges these youth face in the process. Although multiple position papers have called for continuous, coordinated, culturally appropriate, compassionate, family-centered transition programs for youth with special health care needs and have recognized the need for evidence-based models, few data exist on what strategies are most effective. To date, published data on health care transition for HIV-positive youth are limited and include only 2 studies, which considered behaviorally infected youth. In this state-of-the-art review, we discuss the unique transition challenges to consider for this population, including socioeconomic and health insurance status, the special role of the pediatric or adolescent provider as family, stigma and disclosure issues, cognitive development and mental health issues, medication adherence, and sexual, reproductive, and gender health concerns. Future research will need to include the experiences of transition in low-resource settings and examine clinical outcomes and factors that may predict success or failure of the transition process.