The respiratory mucosa is constantly exposed to non-infectious substances that have the potential of triggering inflammation. While many particles are excluded, soluble molecules can reach the epithelium surface, where they can be uptaken by dendritic cells and stimulate an adaptive immune response. Most mucosal responses result in tolerance to subsequent antigen encounters, which is mediated by Foxp3+ regulatory T cells. Genetic and environmental factors, added to the ability of certain allergens to induce innate responses, can predispose to allergic sensitization. In this review we discuss recent advances in the understanding of the mechanisms of tolerance and allergic sensitization to airborne allergens.