Mucosal surface performs various vital functions, such as respiration, absorption, excretion, and reproduction. At the same time, the mucosal surface is inevitably and continuously exposed to various kinds of external foreign antigens derived from food materials, and both commensal and pathogenic bacteria. Generally, tolerance is induced to beneficial antigens including food proteins and commensal bacteria, while protective immunity is induced against pathogenic bacteria and viruses to exclude these harmful pathogens from the entering into our body. Allergic disease is caused by the unexpected hyper-responsiveness against the unharmful antigens which induce generally tolerance. To establish new generation of the preventive and therapeutic strategies for the control of the allergic diseases, the molecular and cellular understanding of the induction of allergic responses at the mucosal compartment of aero-digestive tract needs to be accomplished. In this review, we focus on the recent progress in our understanding of how allergic diseases are developed in the respiratory and intestinal mucosae and applicable strategy for the mucosal allergy vaccine development and immunotherapy.