Pulmonary surfactant is a complex mixture of lipids and protein, which works principally to lower the surface tension of the air liquid interface within the airways and reduce the work of breathing. Deficiency of surfactant in the premature newborn is a principal mechanism in the development of respiratory distress in that population. Over the past decade, surfactant replacement therapy in premature infants has significantly increased survival and decreased the likelihood of significant long-term pulmonary sequelae. Surfactant deficiency in adults with acute respiratory distress syndrome has long been recognized. Although clinical trials of surfactant therapy in adults have not achieved the level of success seen in neonates, multiple recent trials have suggested that success is possible. These results have fueled currently ongoing large clinical trials. The past decade has also revealed that surfactant’s roles are far more numerous than lowering alveolar surface tension. Surfactant also contributes to maintaining the patency of conducting airways, host defense, and mucociliary clearance. The importance of these newly identified roles has been supported by evidence of surfactant dysfunction in airway diseases other than adults respiratory distress syndrome, including asthma and chronic bronchitis. This report reviews the following: (1) surfactant synthesis and composition, (2) surfactant functions, (3) clinical states of surfactant deficiency, and (4) the status of surfactant replacement therapies.