Many human foodborne illnesses can be caused by consumption of foodstuffs (including meat products) contaminated with pathogenic bacteria from animal intestinal contents or hides. Steps that have been taken in the slaughter plant to decrease the spread of foodborne pathogenic bacteria (e.g., hazard analysis and critical control point methods) have been very effective; however, meat products are still the source of foodborne bacterial human illnesses. Increasing numbers of human Escherichia coli O157:H7 illnesses have also been related to contact with animals or to water supplies contaminated by run-off from cattle farms. Thus, strategies that specifically target foodborne pathogenic bacteria in the animal at the farm or feedlot level have great potential to improve food safety and decrease human illnesses. In this review, we describe a broad range of live-animal intervention strategies, both probiotic and antipathogen. Additionally, we examine some of the effects of diet and management strategies on foodborne pathogenic bacterial populations. The use of antibiotics in food animals to decrease foodborne pathogens also will be briefly examined. Overall, the concurrent use of several of these preslaughter intervention strategies could synergistically decrease human illnesses by providing for additional barriers in a multiple-hurdle approach to improving food safety.