There has been a focus for more than 40 years on the bronchial epithelium as an important structure in initiating the physiologic and clinical abnormalities of asthma. This makes sense because the bronchial epithelium is the initial barrier met by all inhaled irritants, toxins, or allergens, and the bronchial epithelium’s response to these noxious stimuli might be important for the subsequent elimination of these stimuli. An initial series of experiments suggested that the loss of the ‘‘tight barrier’’ function of the epithelium with the consequent exposure of irritant nerves, enhanced access to intraepithelial mast cells, or both was the most important epithelial abnormality in asthmatic patients. It was also obvious from bronchial biopsy specimens in adult asthmatic patients that the bronchial epithelium was structurally abnormal, with a marked increased number of goblet cells in the epithelium in asthmatic patients and a suggestion that the epithelium was more friable and easily detached from the basement membrane. Moreover, the bronchial epithelial damage was correlated to the degree of airway hyperresponsiveness in asthmatic patients. Subsequently, it has become clear that the bronchial epithelial cell is not merely a passive player in initiating bronchial responses to allergens or irritants. An example of this is the fact that epithelial cells have the ability to transition into mesenchymal cells, which can contribute to airway remodeling, a characteristic of asthma. This response involves the production of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and TGF-b families and the phenotypic transformation of epithelial cells into fibroblasts, which have the ability to produce extracellular matrix proteins involved in airway remodeling. The characteristic changes of airway remodeling include not only changes to the epithelial cell structure but also deposition of extracellular matrix proteins below the basement membrane, increases in airway blood vessels, and an increase in airway smooth muscle. These changes of airway remodeling occur very early in