It has been established that mucus hypersecretion and decreased mucus clearance contribute to the morbidity of chronic obstructive pulmonary disease (COPD). Indeed, the classic definition of chronic bronchitis relies on determining the frequency and duration of sputum expectoration. Despite the well recognized importance of this symptom, there are few therapies routinely used to decrease the sputum production or to improve clearance. There are fewer well conducted clinical trials of existing medications and this has led many regulatory agencies, notably the Food and Drug Administration (FDA), to refuse to register these medications or approve their sale. Similarly, airway clearance devices and chest physical therapy have not been well studied in COPD. Carefully conducted studies of interventions to improve airway clearance, similar to those done in cystic fibrosis (CF), may help us to identify effective therapies and possibly novel diagnostic tests for the management of COPD.