Respiratory disease is a serious economic problem for swine producers and veterinarians worldwide. The term porcine respiratory disease complex (PRDC) has been used to describe the respiratory disease pattern that has recently emerged. PRDC is multifactorial, involving management factors and multiple pathogens. This article summarizes the pathogenesis and immune response to some of the common respiratory pathogens associated with PRDC, including interactions that lead to the severe respiratory disease associated with PRDC.