Globally, there are 5 million young people aged 15-24 years living with HIV, and many more millions are at risk for HIV acquisition. Compelling research questions exist that require the involvement of young people and other vulnerable populations in HIV-related research in diverse settings around the world. Despite this, there remains a reluctance to involve adolescent participants, including young women, in clinical research. Complex and, at times, contradictory legal and ethical requirements can be a challenge. Ethical benchmarks can be applied to ensure that research meets high-level standards and is planned for appropriately.