The lung is an organ with a large inner surface that is continuously in contact with the environment. Infection of this organ is prevented by several mechanisms. A recently described defence system is collectin-mediated innate immunity of the lung. Collectins are multimeric proteins characterized by carbohydrate recognition domains bound to collagen stalks. Surfactant protein (SP)-A and SP-D are collectins that are present in the epithelial lining fluid of the lung. SP-A interacts with viruses, bacteria and fungi. Furthermore, SP-A binds to various other inhaled glycoconjugates. SP-A receptors on phagocytic cells have been described that are important to ensure rapid pathogen clearance. This innate defence system of the lung may be particularly important during infections in young children when the acquired immune system has not yet become fully established. Also in later life SP-A could be very important to prevent the lungs from infections by pathogens not previously encountered. In addition, SP-A may limit the inflammatory response in the lungs, thus preventing damage to the delicate lung epithelia. Recently, evidence was presented that SP-A may modulate the allergic response to various glycosylated inhaled antigens. The presence of SP-A (and SP-D) in other organs indicates that these collectins may have a general role in mucosal immunity. In this review the interactions of SP-A with a variety of pathogens and its implications are discussed.