Most patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, namely sputum production, increased luminal mucus, submucosal gland hypertrophy and goblet cell hyperplasia. The clinical consequences of hypersecretion are impaired gas exchange and compromised mucociliary clearance, which encourages bacterial colonization and associated exacerbations. However, the extent of the contribution of mucus to pathophysiology of COPD is controversial. Early epidemiological studies found little evidence for the involvement of mucus in the age-related decline in lung function and mortality associated with COPD and concluded that chronic airflow obstruction and mucus hypersecretion were independent processes. Later studies found positive associations between phlegm production and decline in lung function, hospitalization and death. Thus, although not diagnostic for the condition, mucus hypersecretion contributes to morbidity and mortality in certain groups of patients with COPD. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. Unfortunately, ambiguity in clinical studies of mucoactive drugs means that mucolytics are not recommended in clinical management. Future research should determine whether there is an intrinsic abnormality in mucus in COPD, which will determine development of appropriate inhibitors, which in turn can be used in 'proof of concept' and in treatment.