Insufficient hydration at the airway surface can make mucus adherent and poorly cleared. Cough, the major mechanism of mucus clearance in disease, is ineffective when mucus is adhesive. Inhaled mannitol creates an osmotic drive for water to move into the airway lumen. The consequent increased hydration of the airway surface decreases the adherence of mucus to the epithelium, facilitates the coupling of mucus and cilia thereby increasing mucus clearance. Inhaled mannitol also promotes effective coughing and stimulates mucociliary clearance. The beneficial effect of mannitol on mucus and its clearance has been demonstrated in patients with asthma, bronchiectasis and cystic fibrosis. Inhaled dry powder mannitol (Bronchitol™) is promising to be an effective treatment for the clearance of retained airway secretions.