Human immunodeficiency virus (HIV) is transmitted predominantly through sexual intercourse. Research suggeststhat the vaginal epithelium acts as a barrier to HIV transmission, but this epithelium can be disrupted, leading toHIV infection and other sexually transmitted infections. Topical microbicides are considered an effective strategy forHIV prevention, and several candidate drugs are currently in clinical trials. However, significant concerns about drugadherence, efficacy, and safety must be addressed in order to develop a safe and effective microbicide. This paper willprovide an overview of the field and strategies to overcome some of the obstacles facing microbicide development,and briefly discuss a research project that focused on one aspect of preclinical microbicide safety testing.