Recombinant viral vectors based on the human parvovirus, adeno-associated virus (AAV) show considerable promise for human therapeutic application. An important feature that sets this gene transfer system apart from other contemporary virus-based systems is relatively weak induction of innate and cognate immune responses, such that in defined contexts foreign antigens can be expressed long-term in immune competent hosts. This in turn has led to increasing interest in the possibility of exploiting AAV for immune system modulation, including both the induction and avoidance of antigen- specific responses, depending on the therapeutic need. This interest is fuelled by the recognition that the full potential of cell and gene based therapies cannot be realised without parallel developments in therapeutic immune system modulation that allow specific rather than generalised immunosuppression. This review outlines current understanding of AAV immunobiology and explores its potential as a tool for therapeutic manipulation of immune system responses.