Preharvest food safety refers to the concept of reducing the rates of contamination of unprocessed foods with food-borne disease pathogens in order to reduce human exposure and disease. This article addresses the search for effective preharvest food safety practices for application to live cattle to reduce both contamination of foods of bovine origin and environmental contamination resulting from cattle. Although this research has resulted in several practices that significantly decrease contamination by Escherichia coli O157, the effects are limited in magnitude and unlikely to affect the incidence of human disease without much wider application and considerably higher efficacy than is presently apparent. Infection of cattle with E. coli O157 is transient and seasonally variable, likely resulting from a complex web of exposures. It is likely that better identification of the true maintenance reservoir of this agent and related Shiga toxin-producing E. coli is required to develop more effective control measures for these important food- and waterborne disease agents.