Asthma is classically considered the archetypal T_H2 disease, with increased circulating IgE levels and eosinophilic inflammation being caused by increased levels of T_H2-type cytokines. However, this paradigm has been challenged because of the realization that strategies designed to suppress T_H2 function are not effective for all patients. The clinical phenotype of asthma is notoriously heterogeneous and is affected by genetic and environmental exposures in addition to interactions between airway structural cells, including epithelial cells, and the immune system, as well as contributions from cells other than T_H2 cells. A combination of genetic and environmental factors is thought to influence whether inflammation resolves or progresses, and the pulmonary epithelium is increasingly recognized to play a key role in this process. This complex interplay has made it increasingly apparent that immune responses are tailored to the individual patient and determined by the weight of each influence, and thus the label of asthma as a T_H2 disease is too conservative. Indeed, an important concept that needs to be addressed, both in animal models and clinically, is that of T-cell plasticity and how lymphocytic responses are determined by environmental influences.