Bovine respiratory disease (BRD) has a multifactorial etiology and develops as a result of complex interactions between environmental factors, host factors, and pathogens. Environmental factors (eg, weaning, transport, commingling, crowding, inclement weather, dust, and inadequate ventilation) serve as stressors that adversely affect the immune and nonimmune defense mechanisms of the host. In addition, certain environmental factors (eg, crowding and inadequate ventilation) can enhance the transmission of infectious agents among animals. Many infectious agents have been associated with BRD. An initial pathogen (eg, a virus) may alter the animal’s defense mechanisms, allowing colonization of the lower respiratory tract by bacteria.