Genome sequencing, the determination of the complete complement of DNA in an organism, is revolutionizing all aspects of the biological sciences. Genome sequences make available for scientific scrutiny the complete genetic capacity of an organism. With respect to microbes, this means we now have the unprecedented opportunity to investigate the molecular basis of commensal and virulence behavior. We now have genome sequences for a wide range of bacterial pathogens (obligate, facultative, and opportunistic); this has facilitated the discovery of many previously unidentified determinants of pathogenicity and has provided novel insights into what creates a pathogen. In-depth analyses of bacterial genomes are also providing new perspectives on bacterial physiology, molecular adaptation to a preferred niche, and genomic susceptibility to the uptake of foreign DNA, three key factors that can play a significant role in determining whether a species, or a strain, will have pathogenic potential.