Medical anthropologists have been in the forefront of trying to understand socio-cultural and gender barriers related to HIV/AIDS and of bridging cultural perspectives with biomedical ones, contributing to programs related to testing, treatment and prevention. HIV prevention has been in the forefront of critical medical anthropology's efforts to grapple with culture, change and biomedical challenges of the 21st century in view of reaching the Sustainable Development Goals, while also critically testing them. Great advances were made in addressing HIV and AIDS and out of 37.9 million globally living with HIV; 24.5 million are accessing antiretroviral therapy. Nevertheless 1.7 million still became newly infected (2018), of them 510,000 young people (ages 10-24) including 190,000 adolescents (ages 10-19), three-quarters of them girls. In addition, key populations and their sexual partners account for 54% of new HIV infections (UNAIDS 2019). This Panel focuses on the challenges ahead and especially on prevention of HIV among youth and key populations, highlighting innovative and effective culture and gender-sensitive solutions, while acknowledging the changing contexts and attitudes towards HIV and resilient cultural perceptions, such as stigma and discrimination towards people living with HIV. Considering the importance of empowering young people and communities to lead the change towards HIV prevention, the panel welcomes research as well as programs, interventions and best practices focusing on issues such as behavioral change communication related to HIV and comprehensive sexuality education. The contribution of anthropology to the planning and effectiveness will be discussed in view of the most current medical anthropological agendas.