Intensive research efforts for more than two decades have not yet resulted in an HIV vaccine of even moderate effectiveness. However, some progress has been made with other biomedical interventions, albeit on the basis of inconsistent levels of evidence. The male condom, if used correctly and consistently, has been proven in observational studies to be very effective in blocking HIV transmission during sexual intercourse; and, in three randomised trials, male circumcision was protective against HIV acquisition among men. Treatment of sexually transmitted infections, a public health intervention in its own right, has had mixed results, depending in part on the epidemic context in which the approach was assessed. Finally, oral and topical antiretroviral compounds are being assessed for their role in reduction of HIV transmission during sexual intercourse. Research on biomedical interventions poses formidable challenges. Difficulties with product adherence and the possibility of sexual disinhibition are important concerns. Biomedical interventions will need to be part of an integrative package that includes biomedical, behavioural, and structural interventions. Assessment of such multicomponent approaches with moderate effects is difficult. Issues to be considered include the nature of control groups and the effect of adherence on the true effectiveness of the intervention.