The global epidemiology of human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) suggests both reemergent spread among men in resource-sufficient countries since 2000 and emerging epidemics among MSM in resource-limited countries. Both epidemic contexts are evidence of the current limits of prevention of HIV infection in MSM. A range of evidence-based preventive interventions exist, but few new interventions have shown efficacy among MSM. Circumcision has not been investigated for MSM. New interventions are needed. Trials of preexposure prophylaxis are pending and may markedly alter the prevention landscape. For MSM in developing countries, basic services for prevention of HIV infection have yet to reach the large majority of men. Homophobia and discrimination limit access of MSM to prevention services and markedly increase vulnerability, as does criminalization of same-sex behavior. Decriminalization of same-sex behavior is a structural intervention for prevention of HIV infection and has recently been embraced by a nonbinding statement from the United Nations.