A paradigm shift in the management of bacterial diseases of food animals is needed; a shift from pharmacologic interventions to disease risk identification and mitigation. The interaction between disease and its risk factors follows the disease triangle, a conceptual model that incorporates host, pathogen, and environmental factors as a tool to understand different aspects that influence disease. A sustainable approach to bacterial disease mitigation in production settings includes a comprehensive assessment of host, pathogen, and environmental factors of disease to build a prevention platform for multiple syndromes of bacterial disease in cattle. Using bovine respiratory disease as a model, the current chapter will focus on the state of the art of disease prevention in dairy cattle, and investigations into interactions between the host, environment and pathogen which can provide robust information on which to build a prevention platform for multiple syndromes of bacterial disease in cattle.