The absolute requirement of the pulmonary immune system is to limit the inflammatory consequences of inhaled infectious agents while maintaining tolerance to harmless aeroallergens. This tolerance is maintained by a complex network of cells and molecules interacting with lung stromal cells. However, in some individuals there is a breakdown in tolerance to particles such as pollens, animal dander, or dust, resulting in the development of allergic pathology. Emerging evidence suggests that this breakdown in tolerance is influenced by the genetic background of individuals as well as environmental considerations such as early exposure to respiratory pathogens. Further understanding of the mechanisms used by the pulmonary immune system to maintain tolerance might result in exploitation of novel avenues for therapy to treat the growing number of chronic asthmatic patients.