BACKGROUND: Epidemiologic and clinical information in the United States indicate that HIV transmission and acquisition among adolescents and young adults (youth) remain unchanged, without improvement. Interventions to prevent HIV transmission among youth are critically needed, as are interventions to improve adherence to all components of the continuum of care for youth living with HIV. OBJECTIVE: The primary mission of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) is to conduct both independent and collaborative research that explores promising behavioral, microbicidal, prophylactic, therapeutic, and vaccine modalities in HIV-infected and at-risk youth aged between 12 and 24. METHODS: Through the ATN, the National Institutes of Health is supporting HIV interventional research for youth in the United States. RESULTS: The ATN comprises 3 cooperative multiproject research programs and a coordinating center. Each program is led by a network hub and has well-defined research themes to assist, guide, and coordinate HIV research project activities. CONCLUSIONS: ATN activities encompass the full spectrum of research needs for youth, from HIV primary prevention for at-risk youth in the community to secondary and tertiary prevention with clinical management of HIV infection among youth living with HIV experiencing adherence challenges.