There is general consensus that the bacterial agents or products most likely to be used as weapons of mass destruction are Bacillus anthracis, Yersinia pestis, Francisella tularensis and the neurotoxin of Clostridium botulinum. Modern supportive and antimicrobial therapy for inhalational anthrax is associated with a 45% mortality rate, reinforcing the need for better adjunctive therapy and prevention strategies. Pneumonic plague is highly contagious, difficult to recognize and is frequently fatal. Therefore, the development of vaccines against this agent is crucial. Although tularemia is associated with low mortality, the highly infectious nature of aerosolized F. tularensis poses a substantive threat that is best met by vaccine development. Safer antitoxins and a vaccine are required to meet the threat of the use of botulinum toxin as a weapon of mass destruction. In this article, the current status of research in these areas is reviewed.