Mucous hypersecretion is a major cause of airway obstruction in asthma, chronic obstructive pulmonary disease, and cystic fibrosis. EGFR ligands and IL-13 are known to stimulate mucous induction, but the detailed mechanisms of epithelial mucous regulation have not been well defined. In this issue of the JCI, Tyner et al. show, in a mouse model of chronic mucous hypersecretion, that ciliated epithelial cell apoptosis is inhibited by EGFR activation, allowing IL-13 to stimulate the differentiation of these cells into goblet cells, which secrete mucus. In defining this coordinated, 2-step process, we can consider the therapeutic effects of blocking mucous production. This begs the question, Is it possible to reduce airway obstruction in chronic lung disease by inhibiting EGFR activation and/or by inhibiting IL-13?