In this episode of AIDS 2021, we discuss pre-exposure prophylaxis — PrEP — a critical HIV prevention tool for adolescent girls and young women (AGYW) in countries with high HIV burdens. Janet Fleischman speaks with Mitchell Warren, the executive director of AVAC, and two women working with Wits Reproductive Health and HIV Institute in South Africa – Khanyi Kwatsha, a 26-year-old PrEP ambassador, and Elmari Briedenhann, a senior project manager. They discuss the importance of PrEP for AGYW and highlight innovative approaches to better reach this group and to address the inherent challenges of meeting the needs of this population.