According to UNAIDS, the African population accounts for greater than half of persons infected with HIV. Nevertheless, little information exists characterizing HIV in this population. Thus, the natural history and progression of HIV in the African population is virtually undocumented and therefore, poorly understood. Information regarding virtually every aspect of the disease including microbiology, pathogenicity, virulence, and clinical manifestation is based largely on data from select and limited populations. During the HAART-era, we have seen dramatic and significant changes in patterns of NeuroAIDS in patients in clinical cohorts from the United States and Western Europe. These observations have led to increased understanding of the progression of NeuroAIDS and have improved our ability to design treatment regimens to combat CNS complications resulting from HIV. Despite the existence of antiretroviral therapy for HIV, its absence in Africa along with poor treatments for opportunistic infections associated with HIV have become the main sources of neurological morbidity and mortality. In this context, we are presented with a unique opportunity to cultivate and enhance our understanding of the natural history and progression of NeuroAIDS in the African population thereby, better equipping healthcare providers, patients and their families in addressing this epidemic. This concept is particularly important as rapidly improving and more accessible anti-HIV medications and medications for the treatment of opportunistic infections become available to third world countries such as Africa. We believe that it is imperative to foster research, education and training between institutions in the industrialized world and Africa to close the gap in understanding patterns of NeuroAIDS in Africa.