The lung is repeatedly exposed to inhaled particles and pathogens that are cleared by the actions of a multi-component innate host defense system. The pulmonary collectins--surfactant proteins A (SP-A) and D (SP-D)--play important roles in innate host defense by binding and clearing invading microbes from the lung. SP-A and SP-D also influence surfactant homeostasis, contributing to the physical structures of lipids in the alveoli and to the regulation of surfactant function and metabolism. In addition to binding and opsonizing infectious pathogens, SP-A and SP-D bind to the surfaces of host defense cells, promoting or inhibiting immune cell activity through multiple cellular pathways. As a consequence of their physiologic functions, SP-A- and SP-D-dependent pathways are targets for clinical therapies designed to limit the proliferation of microoorgansims and to ameliorate inflammation following pulmonary infection.