The potential application of Yersinia pestis for bioterrorism emphasizes the urgent need to develop more effective vaccines against airborne infection. The current status of plague vaccines has been reviewed. The present emphasis is on subunit vaccines based on the F1 and LcrV antigens. These provide good protection in animal models but may not protect against F1 strains with modifications to the type III secretion system. The duration of protection against pneumonic infection is also uncertain. Other strategies under investigation include defined live-attenuated vaccines, DNA vaccines, mucosal delivery systems and heterologous immunization. The live-attenuated strain Y. pestis EV NIIEG protects against aerosol challenge in animal models and, with further modification to reduce residual virulence and to optimize respiratory protection, it could provide a shortcut to improved vaccines. The regulatory problems inherent in licensing vaccines for which efficacy data are unavailable and their possible solutions are discussed herein.