Surfactant Protein A (SP-A) and D (SP-D) are calcium-dependent collagen-containing lectins, also called collectins, which play a significant role in surfactant homeostasis and pulmonary immunity. The role of SP-A and SP-D in immune defence is well- established. They are known to bind to a range of microbial pathogens that invade the lungs and target them for phagocytic clearance by resident alveolar macrophages. They are also involved in the clearance of apoptotic and necrotic cells and subsequent resolution of pulmonary inflammation. To date, the molecular mechanisms by which SP-A and SP-D interact with various immune cells are poorly understood. In spite of overall structural similarity, SP-A and SP-D show a number of functional differences in their interaction with surface molecules of microorganisms and host cells. The aim of this review is to provide an overview of the current knowledge of ligands and receptors that are known to interact with SP-A and SP-D.