Yersinia pestis, which causes pneumonic plague in healthy individuals, has the potential to be used for biologic warfare. Pseudomonas aeruginosis is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. There is evidence that these two pathogens use a highly homologous virulence mechanism, the type III secretion system. The type III secretion systems of both Yersinia and P. aeruginosa possess a protein named V-antigen which can be used as a target for immunotherapy against bioterrorism and opportunistic infections. This article summarizes the recent progress of V-antigen studies in Yersinia and P. aeruginosa.