It is commonly accepted that airway hyperresponsiveness (AHR) is a chronic airway inflammation although the exact mechanism of its pathogenesis is still unclear. In the past ten years, an epithelial defect hypothesis has gradually gained supports from the main stream. Airway epithelium is no longer considered only as a simple mechanic barrier but an active interface between the inner and outer environment. Bronchial epithelial cells play a critical role in maintenance of homeostasis in the airway local microenvironment through a wide range of physiologic functions including anti-oxidation, exocrine/endocrine secretions, mucus production and antigen presentation under health and stressed/inflamed/injured conditions. It is reasonably hypothesized that disruption of these functional processes or defects in airway epithelium integrity may be the initial steps leading to airway hyperresponsiveness such as in asthma and chronic obstructive pulmonary disease.