The vagina has been used for a long time as a route for drug administration. Vaginal drug delivery has seen recent advances that make it very promising, in particular therapeutic fields such as the prevention of human immunodeficiency virus (HIV) and other sexually transmitted infections, and contraception. This article discusses the main features of vaginal anatomy, physiology, and histology related to drug delivery as well as vaginal drug delivery systems and their evaluation, current usage of the vagina as a route of drug administration, and promising strategies in this field.