The human immunodeficiency virus (HIV) is causing the most destructive epidemic of recent times, having been responsible for the deaths of more than 25 million people since it was first recognised in 1981. This global epidemic remains out of control, with reported figures for 2005 of 40 million people infected with HIV. During 2005 there were 4.9 million new infections, showing that transmission is not being prevented, and there were 3.1 million deaths from the acquired immunodeficiency syndrome (AIDS), reflecting the lack of a definitive cure and the limited access to suppressive antiretroviral treatment in the developing countries that are most severely affected. The current state of the epidemic and the response to date are here reviewed. Present and future opportunities for prevention, treatment and surveillance are discussed, with particular reference to progress towards an HIV vaccine, the expansion of the provision of highly active antiretroviral therapy, and the need to focus control programmes on HIV as an infectious disease, rather than as a development issue.