Patients with the chronic bronchitis form of chronic obstructive pulmonary disease and cystic fibrosis share similar clinical features, including mucus obstruction of airways and the development of chronic/recurrent airways infections that often manifest as disease exacerbations. There is growing evidence that these diseases may have parallels in disease pathogenesis as well, including cystic fibrosis transmembrane conductance regulator dysfunction, mucus dehydration, and defective mucociliary clearance. As progress is made in the development of therapies that target the basic defects that lead to cystic fibrosis lung disease, it is possible that similar approaches could also benefit patients with chronic bronchitis. A deeper understanding of how tobacco smoke and other triggers of chronic bronchitis actually lead to disease, and exploration of the concept that therapies that restore cystic fibrosis transmembrane conductance regulator function, mucus hydration, and/or mucociliary clearance may benefit patients with chronic bronchitis, hold the prospect of significant progress in treating this prevalent disease