Background South Africa has experienced the most severe consequences of the HIV/AIDS pandemic. Every community has been affected in some way, many experiencing huge increases in mortality,particularly before antiretroviral therapies (ART) were readily available. However, the micro-level understanding of the HIV epidemic in South Africa is weak, because of a lack of detailed data for most of the population. This thesis is based on detailed individual follow-up in the Agincourt Health and Demographic Surveillance Site (HDSS) located in the Agincourt subdistrict of Mpumalanga Province and investigates micro-level determinants of HIV epidemiology and the impact of treatment provided. Methods The Agincourt HDSS has followed a geographically defined population since 1992,approximately the time when the HIV/AIDS epidemic first became apparent. This population based surveillance has included capturing details of all deaths, with cause of death determined by verbal autopsy, as well as the geographical location of individual households within the overall Agincourt area. Background information on the roll-out of ART over time was also recorded. Results A comparison immediately before and after the major roll-out of ART showed a substantial decrease in HIV-related mortality, greater in some local communities within the area than others. Individual determinants associated with a decreased risk of HIV/AIDS mortality included proximity to ART services, as well as being female, younger, and in higher socioeconomic and educational strata. There was a decrease in the use of traditional healthcare sources and an increase in the use of biomedical healthcare amongst those dying of HIV/AIDS between periods before and after the roll-out of ART. Conclusions Understanding micro-level determinants of HIV/AIDS infection and mortality was very important in terms of characterising the overall epidemic in this community. This approach will enable public health interventions to be more effectively targeted towards those who need them most in the continuing evolution of the HIV/AIDS epidemic.