Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of antiinflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed over the last decade to assess the usefulness of macrolides in other inflammatory airways diseases, such as cystic fibrosis, asthma, COPD, and bronchiolitis obliterans syndrome. This review summarizes the immunomodulatory properties of macrolides and the results of these recent studies demonstrating their potential for being disease-modifying agents.