Escherichia coli is a ubiquitous bacterium that lives commensally in the guts of most mammals, including man; however, some types of E. coli are pathogenic to humans, including the enterohemorrhagic E. coli (EHEC), of which E. coli 0157:H7 is the most well-known member. Escherichia coli 0157:H7 is a natural member of the gastrointestinal microflora of domestic ruminants (e.g., cattle, goats, sheep) and has been isolated from several wildlife species (e.g., deer, rabbits), and transmission may occur from any of these reservoirs. Although E. coli 0157:H7 is primarily thought of as a foodborne pathogen, recent outbreaks have demonstrated other important routes that lead to human exposure, such as contaminated water and dust. Because E. coli 0157:H7 represents a significant and widespread environmental health hazard, much effort has been directed toward the development of intervention strategies. Because of the relationship between ruminant animals, wildlife, and E. coli 0157:H7, many of the strategies have focused on reducing levels in live animals. In this review article, we examine this virulent pathogen and explore several of the recently developed pre-harvest intervention strategies (including pro-biotic and anti-pathogen strategies, as well as environmental/management changes) and their potential to reduce zoonotic transmission of E. coli 0157:H7 and other EHEC to man.