Dendritic cells (DCs) are generally held responsible for initiating and maintaining allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. Although the epithelium was initially considered to function solely as a physical barrier, it is now seen as a central player in the TH2-cell sensitization process by influencing the function of DCs. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DCs. A better understanding of these interactions, ascertained from human and animal studies, might lead to better prevention and treatment of asthma.