Very little is known about virulence mechanisms of the highly virulent bacterium Francisella tularensis. Specific genetic features of F. tularensis have been obstacles for the development of effective tools for genetic manipulation. However, recent genomic sequencing and large-scale proteomic work have resulted in a substantial increase in the knowledge of F. tularensis. There is also a paucity of information on potential vaccine candidates. Recent work assessing the protective efficacy of the F. tularensis lipopolysaccharide has resulted in important contributions to the understanding of host-protective mechanisms. T-cell-mediated immunity appears to be crucial to protect against virulent F. tularensis strains. Few other vaccine candidates have been identified.