Surfactant is a unique lipid and protein substance made by type II cells in the lung that provides inflation stability, decreases the work of breathing, and has components with innate host defense properties. Surfactant is normally synthesized and secreted into the airspaces of the fetal lung as term approaches, but it can be induced earlier in gestation by fetal exposures to corticosteroids or inflammation. The surfactant deficiency associated with preterm birth can cause severe respiratory failure termed respiratory distress syndrome (RDS), a frequently lethal disease before the availability of clinical surfactants to treat infants. Surfactant components each have complex metabolic characteristics in the premature and mature lung. Term infants can have severe surfactant dysfunction because of rare mutations that disrupt surfactant protein synthesis or processing. The research resulting in the understanding of surfactant metabolism and function and subsequent treatment of RDS is a highlight of progress from science to cure strategies in pulmonary medicine.