Pulmonary surfactants consist of phospholipids and the hydrophobic proteins surfactant protein B and surfactant protein C. These surfactants keep the alveoli in the lung open to the atmosphere. Mutations in the genes encoding these proteins cause a variety of pulmonary syndromes. The pulmonary diseases associated with some of these mutations exemplify the consequences of the accumulation of misfolded proteins in tissue. The hydrophobic surfactant proteins B and C are essential for lung function and pulmonary homeostasis after birth. These proteins enhance the spreading, adsorption, and stability of surfactant lipids required for the reduction of surface tension in the alveolus. Surfactant proteins B and C also participate in the regulation of intracellular and extracellular processes critical for the maintenance of respiratory structure and function. Mutations in the genes encoding surfactant protein B and surfactant protein C ( SFTPB and SFTPC, respectively) are associated with acute respiratory failure and interstitial lung diseases. In this article, we review the current knowledge regarding the structure . . .