Most sexually active youth in the United States do not believe that they are at risk for contracting HIV and have never been tested. Creating safe environments that promote confidentiality and respect, obtaining an accurate sexual and reproductive health assessment, and providing nonstigmatizing risk counseling are key components of any youth encounters. Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing and prophylaxis to adolescent and young adult (youth) patients. In light of persistently high numbers of people living with HIV in the United States and documented missed opportunities for HIV testing, the Centers for Disease Control and Prevention and the US Preventive Services Task Force recommend universal and routine HIV screening among US populations, including youth. Recent advances in HIV diagnostics, treatment, and prevention help support this recommendation. This clinical report reviews epidemiological data and recommends that routine HIV screening be offered to all youth 15 years or older, at least once, in health care settings. After initial screening, youth at increased risk, including those who are sexually active, should be rescreened at least annually, and potentially as frequently as every 3 to 6 months if at high risk (male youth reporting male sexual contact, active injection drug users, transgender youth; youth having sexual partners who are HIV-infected, of both genders, or injection drug users; youth exchanging sex for drugs or money; or youth who have had a diagnosis of or have requested testing for other sexually transmitted infections). Youth at substantial risk for HIV acquisition should be routinely offered HIV preexposure prophylaxis, and HIV postexposure prophylaxis is also indicated after high-risk exposures. This clinical report also addresses consent, confidentiality, and coverage issues that pediatricians face in promoting routine HIV testing and HIV prophylaxis for their patients.