© 2005 by Taylor & Francis Group, LLC. For gas exchange to occur, the epithelium of the lung must maintain a humidified atmosphere with only a thin layer of fluid lining the airway surface. Absorption of fluid out of the airway and alveolar lumen requires active transport of sodium ions (Na+) from the apical surface of the pulmonary epithelium, across the apical and basolateral membranes of epithelial cells, and into the interstitial space and/or bloodstream. Pharmacological inhibitors and genetic manipulations that disrupt Na+ transport result in fluid accumulation within the lung and failure of gas exchange. The importance of Na+ transport in the lung is also demonstrated in several human disease processes, where abnormal absorption of Na+ contributes to the pathophysiology of pulmonary disease.