Airway mucus hypersecretion is a clinical and pathophysiological feature of a number of severe respiratory conditions, including asthma and chronic obstructive pulmonary disease (COPD). The importance of mucus hypersecretion to the morbidity and mortality of asthma is acknowledged, whereas in COPD it appears to affect only certain groups of patients, particularly the elderly and those prone to chest infections. Treatment with compounds that alter mucus is perceived as a therapeutic option, in particular in continental Europe, and numerous compounds have been developed and are available for clinical use worldwide. However, acceptance (or otherwise) of these drugs in guidelines for management of asthma or COPD has been hampered by lack of information from well designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown and is it likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. Current information indicates that the most effective use of mucolytic drugs is long-term therapy for reduction of exacerbations of COPD. Cost-effective treatment would be in patients with poor lung function who have frequent or prolonged exacerbations or are repeatedly admitted to hospital.