Human HIV infection is characterised by great variability in outcome. Much of this variability is due either to viral variation or host genetic factors, particularly major histocompatibility complex differences within genetically diverse populations. The study of non-human primates infected with well characterised simian immunodeficiency virus strains has recently allowed further dissection of the critical role of genetic influences on both susceptibility to infection and progression to AIDS. This review summarises the important role of many host genetic factors on HIV infection and highlights important variables that will need to be taken into account in evaluating effective HIV vaccines.