There is convincing experimental evidence that active sodium and chloride transporters are expressed in the lung epithelium and are responsible for the ability of the lung to remove alveolar fluid at birth as well as in the normal mature lung and when pathological conditions lead to the development of pulmonary edema. The ion transporters described in the alveolar epithelium are epithelial sodium channels, the cystic fibrosis transmembrane conductance regulator, the Na+, K+-ATPase (sodium pump), and aquaporin water channels. In the recent years many experimental studies have shown that the alveolar epithelium plays an important role in alveolar fluid clearance by active vectorial sodium transport. Sodium enters through the apically located amiloride sensitive Na+ channels and it is extruded by the basolaterally located Na+, K+-ATPase consuming ATP with water following iso-osmotically the Na+ gradients. Several drugs that enhance alveolar edema clearance positively affect this mechanism. These include á-adrenergic agonists (epinephrine, nor epinephrine), â-adrenergic agonists (dobutamine, terbutaline, isoproterenol, salmeterol), dopamine, dexamethasone, aldosterone, and several growth factors. The active vectorial sodium and water transport enhanced by specific pharmacological or gene interventions may have a significant role in the resolution of cardiogenic (hydrostatic) or non cardiogenic (increased permeability) pulmonary edema. However, clinical data are lacking yet concerning the importance of the enhancement of lung liquid clearance on survival in patients with acute hypoxemic respiratory failure due to pulmonary edema. Pneumon 2006, 19(1):14-23.