While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary “soil” upon which the “seeds” of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions.