Submucosal glands in the lung play important roles in several hypersecretory lung disease processes, including chronic bronchitis, asthma, and cystic fibrosis. In this context, submucosal glands undergo abnormal growth and differentiation through processes that are poorly understood. To better understand the pathophysiological mechanisms that lead to submucosal gland hypertrophy and hyperplasia in the adult human lung, efforts have been made to dissect the molecular signals and cell types responsible for normal submucosal gland development in the airway. Such studies have revealed a close relationship between progenitor?stem cell phenotypes in the surface airway epithelia and submucosal glands, and thus it has been suggested that submucosal glands serve as a protective niche for surface airway epithelial stem cells. Furthermore, the pluripotent progenitor cells that exist in the surface airway epithelium, which have the capacity to differentiate into ciliated, secretory, intermediate, and basal cells, also have a developmental capacity for submucosal glands. This putative adult stem cell compartment of the airway epithelium has been the focus of research attempting to identify molecular markers for signaling pathways that control stem cell phenotypes and their capacity for proliferation and differentiation following airway injury.