Extraintestinal pathogenic Escherichia coli (ExPEC) possesses virulence traits that allow it to invade, colonize, and induce disease in bodily sites outside of the gastrointestinal tract. Human diseases caused by ExPEC include urinary tract infections, neonatal meningitis, sepsis, pneumonia, surgical site infections, as well as infections in other extraintestinal locations. ExPEC-induced diseases represent a large burden in terms of medical costs and productivity losses. In addition to human illnesses, ExPEC strains also cause extraintestinal infections in domestic animals and pets. A commonality of virulence factors has been demonstrated between human and animal ExPEC, suggesting that the organisms are zoonotic pathogens. ExPEC strains have been isolated from food products, in particular from raw meats and poultry, indicating that these organisms potentially represent a new class of foodborne pathogens. This review discusses various aspects of ExPEC, including its presence in food products, in animals used for food or as companion pets; the diseases ExPEC can cause; and the virulence factors and virulence mechanisms that cause disease.