The AIDS epidemic continues its unrelentless expansion. According to the Joint United Nations Programme on HIV/AIDS, there are more than 40 million people living with HIV, and more than 15,000 new infections occur every day. One approach to curbing HIV is the development of topical microbicidal agents or microbicides. These are compounds designed to protect the body's mucosal surfaces from infection by sexually transmitted disease-causing pathogens, including HIV. Several candidates are in preclinical stages; however, only a handful have been tested in humans for safety, and even fewer are ready for clinical efficacy trials. In this update, we describe microbicide research and development, including preclinical screening algorithms, ideal properties, compounds in the pipeline, and future prospects. This review is based on a previous work, which has been updated to contain new information, especially regarding microbicide candidates in preclinical and clinical stages of development.