The most frequent and best-studied agent of urinary tract infection (UTI) is Escherichia coli, which serves as a useful model pathogen for understanding microbial virulence in relation to UTI pathogenesis. The E. coli strains that cause most UTIs and other extraintestinal E. coli infections represent a highly specialized subset of the total E. coli population. The enhanced virulence potential of such strains, which collectively are known as uropathogenic E. coli or extraintestinal pathogenic E. coli (ExPEC), is thought to be caused mainly by their multiple virulence factors. These virulence factors include diverse adhesins, siderophores, toxins, polysaccharide coatings, and other properties that assist the bacteria in avoiding or subverting host defenses, injuring or invading host cells and tissues, and stimulating a noxious inflammatory response. Although the true evolutionary basis for ExPEC is unknown, the virulence factors of ExPEC serve as useful epidemiologic markers and in the future may provide effective targets for anti-UTI interventions.