Inflammatory mediators play a critical role in the pathogenesis of chronic airway diseases and facilitate the recruitment, activation, and trafficking of inflammatory cells in the airways. Compelling evidence now shows that airway smooth muscle expresses adhesion molecules and secretes inflammatory mediators. Airway myocytes also express a repertoire of immunomodulatory proteins such as Toll-like receptors, chemokines, and cytokines. The underlying mechanisms by which these molecules modulate airway inflammation and the physiological consequences of these molecules are now being elucidated, suggesting that airway smooth muscle plays an important role in orchestrating and perpetuating airway inflammation, remodeling, and fibrosis in chronic airway diseases.