Acute viral and bacterial infections in the lower respiratory tract are major causes of morbidity and mortality worldwide. The proper study of pulmonary infections requires interdisciplinary collaboration among physicians and biomedical scientists to develop rational hypotheses based on clinical studies and to test these hypotheses in relevant animal models. Animal models for common lung infections are essential to understand pathogenic mechanisms and to clarify general mechanisms for host protection in pulmonary infections, as well as to develop vaccines and therapeutics. Animal models for uncommon pulmonary infections, such as those that can be caused by category A biothreat agents, are also very important because the infrequency of these infections in humans limits in-depth clinical studies. This review summarizes our understanding of innate and adaptive immune mechanisms in the lower respiratory tract and discusses how animal models for selected pulmonary pathogens can contribute to our understanding of the pathogenesis of lung infections and to the search for new vaccines and therapies.