Several studies have established that transport of sodium from the air spaces to the lung interstitium is a primary mechanism driving alveolar fluid clearance, although further work is needed to determine the role of chloride in vectorial fluid transport across the alveolar epithelium. Although there are significant differences among species in the basal rates of sodium and fluid transport, the basic mechanism seems to depend on sodium uptake by channels on the apical membrane of alveolar type II cells, followed by extrusion of sodium on the basolateral surface by Na,K-ATPase. This process can be upregulated by several catecholamine-dependent and independent mechanisms. The identification of water channels expressed in lung, together with the high water permeabilities, suggest a potential role for channel-mediated water movement between the air space and capillary compartments, although definitive evidence will depend on the results of transgenic mouse knock-out studies. The application of this new knowledge regarding salt and water transport in alveolar epithelium in relation to pathologic conditions has been successful in clinically relevant experimental studies, as well as in a few clinical studies. The studies of exogenous and endogenous catecholamine regulation of alveolar fluid clearance are a good example of how new insights into the basic mechanisms of alveolar sodium and fluid transport can be translated to clinically relevant experimental studies. Exogenous catecholamines can increase the rate of alveolar fluid clearance in several species, including the human lung, and it is also apparent that release of endogenous catecholamines can upregulate alveolar fluid clearance in animals with septic or hypovolemic shock. It is possible that therapy with beta-adrenergic agonists might be useful to accelerate the resolution of alveolar edema in some patients. In some patients, the extent of injury to the alveolar epithelial barrier may be too severe for beta-adrenergic agonists to enhance the resolution of alveolar edema, although some experimental studies indicate that alveolar fluid clearance can be augmented in the presence of moderately severe lung injury. A longer-term upregulation of alveolar epithelial fluid transport might be achieved by strategies that accelerate the proliferation of alveolar type II cells repopulating the injured epithelium in clinical lung injury. More clinical research is needed to evaluate the strategies that can upregulate alveolar epithelial fluid transport with both short-term therapy (i.e., beta-agonists) and more sustained, longer-term effects of epithelial mitogens such as keratinocyte growth factor. These approaches may be useful in reducing mortality in the acute respiratory distress syndrome.