Clinical reports of areas of damaged airway epithelium associated with shed epithelial cells in bronchoalveolar lavage fluid, aberrant epithelial repair processes, and altered cytokine and growth factor release have highlighted some fundamental differences between the airway epithelium in individuals with and without asthma. However, the consequences of these epithelial changes are not clearly defined, and may be difficult to assess in the clinic. In this Review, we answer the two questions. (1) What in vivo models and methods have been used to inform us about airway epithelium damage, repair, and immune responses? Our response focuses on genetic influences as well as allergen exposure, environmental/chemical, and mechanical models. (2) How can we improve on existing mouse models to understand changes in airway epithelium biology in asthma? In answering the second question, we include exciting recent studies that have combined multiple exposure methods and/or epithelium-centric outcome measurements. By addressing these two questions, we propose that future interrogation of epithelial responses of both existing and nascent mouse models may provide greater understanding of the mechanisms underlying airway inflammation and remodeling in asthma with hope of generating novel therapeutic targets.