The transmission of HIV and the progression of HIV disease are influenced not only by a large number of human host factors, but also by certain correlates of the ever fluctuating virus quasispecies. The present review article aims at providing the current state of knowledge as well as an in-depth critical discussion of recent developments on the potential effects of HIV subtype, phenotype and attenuation on HIV disease. Despite the extensive research, several questions regarding the precise role that each of these correlates plays in human AIDS pathogenesis remain unanswered. Unraveling these roles is expected to aid the continued quest for truly effective antiretroviral drug regimens and preventive vaccines.