The worldwide epidemic of HIV continues to expand in many regions of the world, particularly in southern Africa, South and Southeast Asia, East Asia and Eastern Europe and Central Asia. Estimates are that at the end of 2005 there were 38.6 million persons living with HIV infection and that 4.1 million new infections and 2.8 million deaths from HIV occurred during the year. Regionally different patterns predominate from generalized heterosexual epidemics in sub-Saharan Africa and parts of the Caribbean to mixes of epidemics in which transmission among injection drug users, their sexual partners, commercial sex workers and their partners intersect. Multilateral and bilateral antiretroviral access campaigns, such as the World Health Organization's 3 x 5 initiative, have resulted in broader access to live-saving therapy for infected persons in low- and middle-income countries, but several million infected people who are clinically eligible for antiretroviral therapy remain untreated. The public health challenge worldwide is to keep the uninfected and to treat and care for those who have already been infected.