Asthma research has focused primarily on allergic pathways on the basis that the majority of asthma is associated with atopy, the recruitment of the Th2-type T cell, the cytokines, and the chemokines that are released on exposure to allergens, and the IgE pathway. However, despite considerable investment by industry, targeting these pathways has not resulted in new treatments being developed beyond blockade of cysteinyl leukotrienes and IgE and improvements in inhaled corticosteroids and beta(2)-adrenoceptor bronchodilators. Increasingly, it is recognized that asthma is a heterogeneous disorder, and while important, allergen sensitization is only one component of the disease, with many other environmental and genetic factors playing a role. In addition, these factors act locally on a susceptible airway epithelium that is both structurally and functionally deficient. It may be worthwhile to focus on increasing the resilience of the airways to environmental insults in addition to improving strategies that modify adaptive immunity or suppress inflammation.