The availability of the genome sequences of different strains of Francisella tularensis is having a major impact on a wide range of research projects, from understanding the biology of this organism to devising vaccines and diagnostics. Comparative genomics and molecular typing methods suggest that the four different subspecies of F. tularensis are genetically distinct groups. Although there is a high degree of nucleotide identity between strains, there are numerous DNA rearrangements. IS elements appear to have played a major role in these chromosomal rearrangements. The different subspecies of F. tularensis appear to have evolved by vertical descent from a common ancestor, probably F. tularensis subspecies novicida. Comparative genomic and proteomic studies have revealed possible reasons for the different virulence of different strains and a range of candidate virulence genes have been identified including those located on the Francisella pathogenicity island. Proteomic studies have identified proteins which are produced at elevated levels in vivo, and proteins which are recognized by immune or convalescent sera. These proteins might be exploited as components of vaccines or diagnostic systems.