Microbicides are vaginally or rectally applied drugs that inhibit HIV and other sexually transmitted pathogens. About 30 microbicidal products are being studied in preclinical and clinical trials. Data from in vitro, animal, and in vivo investigations with candidate microbicidal compounds support a proof of concept, although large-scale clinical trials will determine efficacy. Because there are multiple targets for HIV infection in the genital tract, synergistic combinations of microbicides will probably offer the greatest protection for non-HIV-infected persons and might decrease transmissibility when used by those infected with HIV.