The lung is constantly exposed to invading particulate matter and potential pathogens. To cope with this pressure, the lung has evolved a sophisticated, multitiered defense mechanism designed to clear offending agents while inducing a minimum amount of concomitant inflammation. Mechanical defense mechanisms first attempt to remove material physically from the tracheobronchial tree. Particulate matter and pathogens that circumvent this first line of defense are ingested by resident and recruited phagocytes in the lower respiratory tract and alveoli. If phagocytic defenses are impaired or overwhelmed, specific immune mechanisms become operational and lead to the generation of delayed-type hypersensitivity (granulomatous), cytotoxic, and humoral (antibody) responses. Congenital or acquired impairment of pulmonary host defenses can occur at any of these steps. Impairment of a particular component of pulmonary host defense is usually associated with a characteristic spectrum of infectious and noninfectious pulmonary complications. Thus, understanding all the components of pulmonary host defense and how to evaluate them will greatly aid the physician who cares for immunocompromised patients with lung disease.