We have outlined the myriad of roles, both proven and suspected, of epithelial cells in airway inflammation in general and CRS in particular. There is little doubt that these remarkable cells are essential for host defense, tissue responses to injury and threats, and inflammation that cause disease. We believe that many of these responses are likely to be amenable to the development of new therapies for CRS. As we acquire more information on the signaling processes that drive the protective responses in epithelial cells, we will improve our chances of developing approaches to enhance these responses without triggering deleterious inflammatory responses. Enhanced clearance of fungi and bacteria by local immune responses would likely be beneficial in reducing disease. As we better understand the signals that epithelial cells give and get from DCs, B and T lymphocytes, new opportunities for productive intervention will arise.