The HIV/AIDS pandemic has become part of the contemporary global landscape. Few predicted its effect on mortality and morbidity or its devastating social and economic consequences, particularly in sub-Saharan Africa. Successful responses have addressed sensitive social factors surrounding HIV prevention, such as sexual behaviour, drug use, and gender equalities, countered stigma and discrimination, and mobilised affected communities; but such responses have been few and far between. Only in recent years has the international response to HIV prevention gathered momentum, mainly due to the availability of treatment with antiretroviral drugs, the recognition that the pandemic has both development and security implications, and a substantial increase in financial resources brought about by new funders and funding mechanisms. We now require an urgent and revitalised global movement for HIV prevention that supports a combination of behavioural, structural, and biomedical approaches and is based on scientifically derived evidence and the wisdom and ownership of communities.