The clinical syndrome of bovine respiratory disease (BRD) continues to be a major challenge in bovine production systems. We are challenged by our ability to predict morbidity in groups of cattle, our ability to accurately diagnose and provide a prognosis for individual cases, and our ability to evaluate the results of preventive and therapeutic interventions in the field when production system data are the sole basis for analysis. However, we are fortunate to have perhaps the highest quantity and quality of negative-controlled, prospective, randomized, and masked clinical trial data for any disease in veterinary medicine. It is nevertheless important to recognize that case definitions in these studies may not be consistent or necessarily externally relevant, and that production data in these studies are often missing.