An important part of biodefense is the optimization of current therapy and the development of new therapeutic options for the treatment of the diseases most likely encountered in the form of biological weapons. Guidelines for the prevention and treatment of anthrax, plague, tularemia and botulinum toxin intoxication are reviewed. The strategies in development for the prevention of anthrax focus primarily on active and passive immunization against protective antigen, because of its central role as a toxin delivery module. Novel vaccine strategies for plague, tularemia and botulism are also reviewed.