The AIDS epidemic presents a complex of issues that require global answers, involving entire societies. The only sustainable solution is to include all sectors of society in a multidisciplinary collaboration, within which the formal education system plays a key role in delivering a comprehensive response to the disease at the national level. Moreover, in order to be effective, governments must work in collaboration with parents, religious leaders, and community members. This article describes eight key issues that must be addressed to establish a successful HIV/AIDS education curriculum. It also provides examples of best practices from three countries. First, HIV education in schools should adopt a human rights perspective and address stigma and discrimination against people living with HIV (PLHIV). Second, gender issues should be fully integrated into messages about the disease and the whole community should be sensitized on this topic. Third, national curricula must be designed in respect of religious perspectives; the most successful ones will include religious leaders in the process. Fourth, the language and content used in designing education materials for schools must be culturally sensitive, as local traditions can influence the transmission of HIV; those developing curricula should explore the best ways to incorporate positive traditions into formal education initiatives. Fifth, governments are responsible for providing comprehensive and adapted messages about the disease to children and youth in school settings; they must develop a national strategic policy on it and establish specific measures established to protect PLHIV. Sixth, the family plays the primary role in providing information to children on sexuality and HIV-related issues, even if parents and children sometimes find it hard to talk about. Parents must be informed so they can play a more active role in educating their children in this area. Seventh, teachers and administrators are central to effective HIV education; as they often complement parents' roles, they need to be trained at pre- and in-service levels on these issues, including sexuality. Finally, children and young adults should learn about sexuality and HIV and AIDS at various stages throughout their development. It is crucial to adapt the content to the age and knowledge level of the target group.