Despite considerable strides made in the fight against HIV/AIDS in Africa, it still remains a formidable challenge in the areas of public health and general development in the continent. This entails that there is no gainsaying the need for continued concerted efforts at addressing the menace of the pandemic. Without doubt, Faith-Based Organizations (FBOs) have emerged as critical agencies of health provisioning in Africa especially with reference to HIV/AIDS and imperative avenues for fighting the pandemic in Africa. The aim of this chapter is to assess the role of FBOs in South Africa in the response and more critically how such roles can be repositioned and enhanced to contribute more meaningfully to the overall national response.