Since the start of the human immunodeficiency virus (HIV) pandemic, numerous biomedical advances have caused the social-work response to shift from management of a crisis to prevention of an incurable, but treatable chronic disease. About 1.3 million people in the United States and more than 33 million people worldwide are estimated to be living with HIV. Rates of incidence in impoverished, marginalized communities are highest, with the rates continuing to increase among young African American gay and bisexual men. Other communities at high risk are people who are incarcerated, engage in sex work or other kinds of exchange sex, and participate in risky injection-drug use. Minority groups are often impacted because of reduced access to quality medical care and HIV testing. Social workers in HIV prevention work are challenged to educate clients and communities on the sexual risk continuum, provide more interventions that are culturally tailored for disadvantaged at-risk groups, and implement evidence-based HIV prevention and testing programs worldwide. The National HIV/AIDS Strategy now provides structure to funding opportunities for HIV prevention programs, and there is disparate access to effective treatments worldwide for those living with HIV.