In addition to their well-known antimicrobial activity, macrolides possess immunomodulatory properties that may confer beneficial effects to patients with respiratory diseases associated with chronic inflammation. These properties include attenuation of inflammatory responses in the lung, mucoregulatory properties, and effects on bronchial responsiveness. Macrolides increase mucociliary clearance, improve sinusitis symptoms, and decrease nasal secretions and polyp size in patients with sinusitis. They also have been shown to modify the inflammatory response associated with chronic sinusitis. In patients with asthma, macrolides have been reported to reduce airway hyperresponsiveness and improve pulmonary function, and have historically been selected for their “steroid-sparing” effect. Preliminary data from studies of patients with COPD have shown improvements in symptom scores and FEV1 after macrolide treatment. As biological response modifiers, macrolides have the potential to improve the outcomes of patients with inflammatory airway diseases. Large scale, placebo-controlled clinical trials designed to assess long-term efficacy and safety in these diseases are warranted.