The study begins with an overview of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement and its flexibilities, delineating the legal requirements of the TRIPS agreement regarding their use. It then examines the challenges entailed in the beneficial interpretation and implementation of the TRIPS agreement at both the national and regional levels under the auspices of African Regional Intellectual Property Organization (ARIPO) and African Intellectual Property Organization (OAPI). The next section reviews the domestic antiretroviral (ARV) production experiences of Zimbabwe, Kenya, South Africa, and Ghana with an eye for evaluating the option of sustainable local production. The study is based on existing literature and on interaction with various key players and resource persons in government institutions, the private sector, and civil society groups, especially nongovernmental organizations (NGOs) at the national level. Information was gathered from officials of the regional patent institutions, OAPI and ARIPO, along with official documents of these institutions. International organizations involved in HIV/AIDS work in Sub-Saharan Africa (SSA) also provided input. The study was conducted under considerable time and logistical constraints, making it difficult to meet and interview all the persons that the authors wished to consult during travel across the African continent. Another limitation was the lack of an easily accessible database on ARVs and other HIV/AIDS medicines being used in Africa, their patent status, and their relative prices. National drug procurement bodies were often reluctant to divulge information on prices and quantities of medicines obtained.