Bacterial virulence factors enable a host to replicate and disseminate within a host in part by subverting or eluding host defenses. The use of genomic techniques has led to the identification of new virulence factors that may serve as targets for new therapies. These putative virulence factors must be rigorously evaluated with in vitro and in vivo studies with an awareness of the technical limitations of each approach as well as an assessment of the prevalence of this factor in clinical bacterial isolates retrieved from appropriately controlled epidemiologic studies.