While it has long been recognized that the mucosal and systemic immune systems function semiindependently, until fairly recently, understanding of aeroallergen hypersensitivities derived principally from studies of systemic immune regulation. Nonetheless, tolerance and hypersensitivities to airborne allergens are likely to be driven primarily, if not exclusively, by immunological events taking place within the lungs and their associated lymphoid tissues. Therefore, this review will focus on the role of the airways in the prevention, development, and treatment of respiratory allergic diseases. I will first consider how the immunological immaturity of infancy may contribute to the genesis of respiratory allergic diseases. Current understanding of the mechanisms that promote airway allergen tolerance and those that mediate CD4 cell differentiation will then be discussed. Subsequent sections will review how airway exposures to allergens and man made and natural adjuvants influence local immune homeostasis and host risk for developing respiratory allergic diseases. Finally, I will consider how interventions that target airway immunity might be utilized for the prevention and treatment of aeroallergen hypersensitivities.