Surfactant protein A (SP-A) is a highly ordered, oligomeric glycoprotein that is secreted into the airspaces of the lung by alveolar type II cells and Clara cells of the pulmonary epithelium. Although research has shown that SP-A is both a calcium-dependent phospholipid-binding protein that affects surfactant structure and function and a lectin that opsonizes diverse microbial species, our understanding of the physiologically relevant roles of SP-A in the lung remains incomplete. My review focuses on the putative biological functions of SP-A that are supported by experiments in mammals and on the structural basis of SP-A function.