 Our current understanding of the pathogenesis of CF lung disease stems from data that demonstrate the presence of airway surface liquid ASL dehydration in CF. ASL dehydration in CF is caused by defective chloride secretion through the cystic fibrosis transmembrane regulator CFTR and increased sodium reabsorption through the epithelial sodium channel ENaC. ASL dehydration, in turn, interferes with the mucociliary clearance apparatus, causing a breach in a critical line of lung host defense. A number of novel therapeutics are now being developed to address this basic defect of disease, including the use of inhaled hypertonic saline. 