The skin has long been recognized as an attractive target for vaccine administration. A number of clinical studies have tested the epidermal and dermal routes of delivery using a variety of vaccines over the years. In many cases, cutaneous administration has been associated with immunological benefits, such as the induction of greater immune responses compared with those elicited by conventional routes of delivery. Furthermore, there is a growing body of evidence to suggest that such benefits may be particularly important for certain higher-risk populations, such as the elderly, the immunocompromised and cancer patients. Despite the potential advantages of vaccination via the skin, results have sometimes been conflicting and the full benefits of this approach have not been fully realized, partly due to the lack of delivery devices that accurately and reproducibly administer vaccines to the skin. The 5-year outlook, however, appears quite promising as new cutaneous delivery systems advance through clinical trials and become available for more widespread clinical and commercial use.