The biophysical properties of airway secretions are largely determined by the polymeric components. In normal airway mucus, the gel-forming mucins, MUC5AC and MUC5B, are responsible not only for the viscoelastic properties essential for clearance and protecting the airway epithelium from invaders and water evaporation. With chronic airway infection, inflammatory cell necrosis leads to a predominance of polymeric DNA and F-actin. There is almost no mucin in the sputum of patients with established cystic fibrosis lung disease. Sputum viscoelastic and surface properties determine how well secretions can be cleared by cilia or cough. In this mini-Symposium on Airway Clearance in Cystic Fibrosis, the physiology of CF secretion structure and rheology is discussed in the context of medications and physical maneuvers for enhancing sputum clearance.