Fewer than one million HIV infected individuals are currently receiving anti-retroviral therapy. The limitations of such treatment have underscored the need to develop more effective strategies to control the spread and pathogenesis of HIV. Typically, naturally occurring protective immune responses provide the paradigm for such development. It is now clear however that HIV can utilise the millieu of an activated immune system to its own replicative advantage. Mobilisation of the immune response, intended to thwart the virus, may instead fuel its dissemination, ’immune escape’ and spread. The immense genetic variation of HIV contributes to lack of immune control and the development of progressive disease in the majority of infected, untreated individuals. Further delineation of the intimate interactions between the HIV and the immune system will be critical and recent advances in this direction are discussed. The limitations of such treatment have underscored the need to develop more effective strategies to control the spread and pathogenesis of HIV. Typically, naturally occurring protective immune responses provide the paradigm for such development. It is now clear that that HIV can utilise the millieu of an activated immune system to its own replicative advantage. Mobilization of the immune response, intended to thwart the virus, may instead fuel its dissemination, ’immune escape’ and spread. immense genetic variation of HIV contributes to lack of immune control and the development of progressive disease in the majority of infected, untreated individuals. Further delineation of the intimate interactions between the HIV and the immune system will be critical and recent advances in this direction are discussed .