Allergic sensitization to inhaled antigens is common but poorly understood. Although lung epithelial cells were initially merely regarded as a passive barrier impeding allergen penetrance, we now realize that they recognize allergens through expression of pattern recognition receptors and mount an innate immune response driven by activation of nuclear factor kappa B. On allergen recognition, epithelial cells release cytokines, such as IL-1, IL-25, IL-33, thymic stromal lymphopoietin, and GM-CSF, and endogenous danger signals, such as high-mobility group box 1, uric acid, and ATP, that activate the dendritic cell network and other innate immune cells, such as basophils and type 2 innate lymphoid cells. Different allergens stimulate different aspects of this general scheme, and common environmental risk factors for sensitization, such as cigarette smoke and diesel particle exposure, do so as well. All of this is influenced by genetic polymorphisms affecting epithelial pattern recognition, barrier function, and cytokine production. Therefore, epithelial cells are crucial in determining the outcome of allergen inhalation.