Nanopharmaceuticals have the potential to revolutionise medical treatment by permitting the design of more potent, less toxic “smart” therapeutics, ultimately leading to personalised medicine. This review summarises the challenges and potential uses of nanodelivery system for the topical drug therapy of vaginal diseases. The vaginal route of drug administration remains a challenge in the development of novel drug therapies, including nanomedicines. We attempted to provide an unbiased overview of currently investigated nanodelivery systems, some of which remain to be extensively studied under laboratory conditions, and some of which are already in clinical trials. Most nanodelivery systems are aimed at improving the treatment of vaginal infections, including HIV prevention. Promising new approaches in nanopharmaceutical design are discussed in this review, as well as the controversies related to mucoadhesiveness of nanopharmaceuticals.