The normal tracheobronchial epithelium is continuously renewing itself: cells are lost and replaced by the proliferation and differentiation of stem cells. The proliferation and differentiation of these cells have to be tightly controlled in order to maintain the normal structure of the epithelium. A variety of biological and biochemical processes are involved in controlling the proliferation and differentiation of the tracheobronchial epithelium. Since the trachea and bronchus are comprised of a heterogeneous cell population, interactions between the different cell types are of crucial importance not only in controlling the normal maintenance of this tissue but also in the regulation of repair processes following injury and morphogenesis during lung development. A variety of factors, including several polypeptide growth factors and cytokines, have been identified that regulate positively or negatively the growth and differentiation of tracheobronchial epithelial cells by autocrine or paracrine mechanisms. Retinoids are another group of regulatory factors that appear to play a crucial role in controlling cell proliferation and differentiation in the tracheobronchial epithelium. Recently, many advances have been made in understanding the action of these agents in these cells. Alterations in the balance between growth and differentiation regulatory factors appear to play an important role in several pathophysiological changes such as hyperplasia, fibrosis, and neoplasia.