Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.