Several potential reservoirs for the Escherichia coli strains that cause most human extraintestinal infections (extraintestinal pathogenic E. coli; ExPEC) have been identified, including the human intestinal tract and various non-human reservoirs, such as companion animals, food animals, retail meat products, sewage, and other environmental sources. Understanding ExPEC reservoirs, chains of transmission, transmission dynamics, and epidemiologic associations will assist greatly in finding ways to reduce the ExPEC-associated disease burden. The need to clarify the ecological behavior of ExPEC is all the more urgent because environmental reservoirs may contribute to acquisition of antimicrobial resistance determinants and selection for and amplification of resistant ExPEC. In this chapter, we review the evidence for different ExPEC reservoirs, with particular attention to food and food animals, and discuss the public health implications of these reservoirs for ExPEC dissemination and transmission.