BACKGROUND Oral mucolytics are now recommended in some treatment guidelines for the management of chronic obstructive pulmonary disease (COPD). This article reviews the evidence for their use and their possible benefits. METHODS The review is based upon peer reviewed publications relating to the use of mucolytics in COPD cited in PubMed. RESULTS Much of the published evidence is of somewhat poor quality and many studies include patients with both chronic bronchitis and COPD. Mucolytics reduce exacerbations by up to 0.8 exacerbations per year, but have little additional benefit in those on standard maximum therapy. RESULTS Data that mucolytics improve symptoms, alter mucus or impact health-related quality of life in COPD patients receiving other standard therapy are unconvincing. In those on little or no other treatment, they may reduce exacerbation rate. CONCLUSIONS The use of mucolytics to treat acute exacerbations is promising. CONCLUSIONS Head-to-head trials of mucolytics versus long-acting bronchodilators and/or inhaled corticosteroids are lacking. Even in patients with severe COPD who remain symptomatic despite maximal inhaled therapy the role of mucolytics remains unproven.