Many adolescents are at high risk for HIV infection, and those who are infected or at-risk commonly present to the ED, often as their only or frequent source of care. It is important to consider routine screening and to have a high index of suspicion for AHI in this setting. If a diagnosis of HIV infection is made, immediate linkage to care with a specialist in adolescent and young adult HIV infection should be prioritized. For the known HIV-infected patient, management must consider unique possibilities of OIs, IRIS, and medication side effects. For any patient on ART, drug-drug interactions must be noted as part of any treatment plan. If a young person presents with a recent sexual or needlestick exposure of concern, every effort to prescribe and ensure follow-up for PEP should be made. It is essential for physicians to understand and comply with local regulations regarding HIV testing and adolescents' rights for associated confidential care. Finally, physicians who see adolescents in acute care settings have a tremendous opportunity to make a difference in ensuring improved health outcomes for youth living with HIV and to prevent new infections.