Southern Africa remains the region most severely affected by the human immunodeficiency virus (HIV) epidemic. The nine countries with the highest HIV prevalence worldwide are all located in this subregion. With about 5.5 million people living with HIV/acquired immunodeficiency syndrome (AIDS), South Africa has the largest population of HI infected individuals, representing a quarter of the burden of HIV infection in sub-Saharan Africa [1]. Heterosexual exposure is the primary mode of transmission and HIV subtype C the dominant subtype. The HIV epidemic in South Africa has been characterized by a rapid spread of HIV in the general population in the period 199-2000, with a substantial geographical variation across the country. Unfortunately, South Africa's response to the evolving epidemic during the past decade was marked by denial and lack of political will, and it is only recently that decisive action has been taken to address this enormous challenge [2,3]. See Chapter 21, Parts 1 and 2, on HIV/AIDS surveillance in India and Russia, respectively.