The AIDS epidemic in Africa remains an urgent health crisis. Non-governmental organizations (NGOs) in Africa play a critical role in the delivery of HIV prevention services and assistance to persons living with AIDS. African NGOs are conducting numerous HIV prevention programs with several at-risk populations, yet their efforts have only rarely been systematically documented. To address this gap in the literature, the authors surveyed one NGO in each of 29 African countries regarding their HIV prevention activities and populations served. This report provides details concerning HIV prevention activities across the continent and describes in detail innovative programs from Togo and South Africa. NGOs in the present sample operate with modest budgets and small staff sizes, yet conduct programs that reach large segments of their communities. NGOs were most likely to report community-level interventions such as peer-education or community outreach. Faced with an epidemic where the main transmission occurs via heterosexual activity, African NGOs were most likely to direct their attention to the general public and to youth. NGOs in Africa are struggling to implement sustainable, cost-effective programs with few resources. Strengthening the infrastructure and capacity of these key agencies is crucial to fighting the AIDS epidemic in Africa.