Gene therapy remains an attractive form of treatment for a variety of diseases, both inherited and acquired. Recent experience in clinical gene therapy has highlighted important safety issues pertaining to gene delivery in humans. As such, the choice of gene delivery system for individual applications is fundamentally important and must afford efficiency and safety. Adeno-associated viral (AAV) vectors have unique potential among the repertoire of vector systems currently available. Here, we highlight recent developments to suggest that AAV vectors will play a key role in the future deployment of genetic medicine in humans.