Important immunomodulatory properties of 14- and 15-membered macrolides may benefit patients with respiratory diseases associated with chronic inflammation. These properties include decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of transcription factors leading to decreased proinflammatory cytokine production, downregulation of adhesion molecule expression, inhibition of microbial virulence factors including biofilm formation, reduced generation of oxygen-free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance. Chronic, low-dose macrolides have dramatically improved survival in patients with diffuse panbronchiolitis (DPB). Given the overlap in pathogenesis between DPB and other chronic respiratory diseases, macrolides are being investigated for cystic fibrosis, asthma, chronic bronchitis, chronic sinusitis, and chronic obstructive pulmonary disease. Preliminary data (largely from open-label trials) are promising, but conclusive results are needed.