Bovine respiratory disease (BRD) is a multifactorial disease complex caused by factors including stress, primary viral infection and a concurrent bacterial infection. Stress includes environmental and managemental factors especially inadequate ventilation, comingling of calves, over-crowding and poor nutrition. Exposure to different kinds of pathogens like bovine herpes virus 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BoCV), infectious bovine rhinotracheitis (IBR), Mycoplasma bovis, Mannhaemia haemolytica, Pasteurella multocida and Histophilus somni causes BRD in immunocompromised cattle calves. Failures of transfer of passive immunity in calves predispose them to secondary bacterial infection. Immunohistochemistry (IHC) and molecular diagnostic tests like PCR with histopathological examination is more in use as compared to the traditional viral isolation and bacterial culture. Often thoracic auscultation and ultrasonography are employed for the primal BRD diagnosis in pre-weaned calves. This article deals with the various viral and bacterial pathogens associated with BRD.