The development of new generation vaccines is an imperative tool to counteract accidental or intended release of bio-threat agents, such as Bacillus anthracis, Yersinia pestis and variola virus, and to control natural outbreaks. In the past few years, numerous data accumulated on the immunogenicity and safety of plant-made vaccines against bio-security-related organisms. In addition, expression levels achieved for these antigenic proteins are practical for the production of sufficient material for large-scale vaccination programs. These data demonstrated that the plant-based approach is feasible for manufacturing recombinant vaccines against bio-terror agents that could be mass-produced at reasonable cost.