Pulmonary surfactant proteins A and D (SP-A and SP-D) belong to the collectin subgroup of the C-type lectin superfamily along with mannose-binding protein (MBP) and conglutinin. Phospholipids are also ligands for collectins, in addition to carbohydrates and glycosphingolipids. SP-A binds dipalmitoylphosphatidylcholine, and SP-D and MBP bind phosphatidylinositol. SP-A also interacts with alveolar type II cells, implicating SP-A in surfactant phospholipid homeostasis. We analyzed an epitope for anti-SP-A monoclonal antibodies that block SP-A-specific functions using a phage display peptide library and SP-A/MBP chimeric proteins. We also investigated the regions of SP-A and SP-D that are required for ligand interactions using SP-A/SP-D chimeras. Lung collectins play key roles in the innate immune system of the lung which is critical for immediate antibody-independent host defense. We have found that SP-A exhibits different interactions with distinct serotypes of lipopolysaccharides and affects differently their elicited cellular responses by a direct interaction with the lipopolysaccharide receptor CD14. In addition to the basic aspects, lung collectins as clinical markers will be discussed.