Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a human pathogen responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Conventional antimicrobials trigger an SOS response in EHEC that promotes the release of the potent Shiga toxin that is responsible for much of the morbidity and mortality associated with EHEC infection. Cattle are a natural reservoir of EHEC, and approximately 75% of EHEC outbreaks are linked to the consumption of contaminated bovine-derived products. This review will discuss how EHEC causes disease in humans but is asymptomatic in adult ruminants. It will also analyze factors utilized by EHEC as it travels through the bovine gastrointestinal (GI) tract that allow for its survival through the acidic environment of the distal stomachs, and for its ultimate colonization in the recto-anal junction (RAJ). Understanding the factors crucial for EHEC survival and colonization in cattle will aid in the development of alternative strategies to prevent EHEC shedding into the environment and consequent human infection.