Significance Mucoobstructive lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis, are characterized by intrapulmonary accumulations of hyperconcentrated mucus. Ultimately, mucus accumulation in disease reflects the failure of the major rescue mucus clearance pathway, i.e., cough. Studies were performed to understand how abnormal mucus and its interactions with the cell surface produce a failure of cough clearance. These studies identified mucus concentration-dependent cohesive and adhesive properties, governed by mucus viscous energy dissipation, as rate limiting for the efficiency of cough clearance. Parallel studies designed to restore mucus cough clearability identified reduction of mucus concentration (rehydration) and use of mucolytics as additive and promising therapeutic strategies.