The airway epithelium is composed of a heterogeneous population of cells. This epithelial layer is not only a physical barrier but also a target responding to a variety of inflammatory mediators. These cells can respond by releasing contracting and relaxing factors to modulate airway responsiveness. They can also metabolize some of the inflammatory mediators. Epithelial damage is a consistent feature of some respiratory conditions, but whether or not such damage contributes to airway disease is for the moment unknown. This review summarizes the literature on the known and proposed roles of the epithelium in the modulation of the airway smooth muscle tone.