Enterohemorrhagic Escherichia coli O157:H7 is a major food-borne pathogen causing severe disease in humans worldwide. Healthy cattle are a reservoir of E. coli O157:H7 and bovine food products and fresh produce contaminated with bovine waste are the most common sources for disease outbreaks in the United States. E. coli O157:H7 also survives well in the environment. The ability to cause human disease, colonize the bovine gastrointestinal tract, and survive in the environment, requires that E. coli O157:H7 adapt to a wide variety of conditions. Three major virulence factors of E. coli O157:H7 have been identified including Shiga toxins, a pathogenicity island called the locus of enterocyte effacement, and an F-like plasmid, pO157. Among these virulence factors, the role of the pO157 is least understood. This review provides a board overview of E. coli O157:H7 with an emphasis on the pO157.