OBJECTIVE: To review the concept that asthma comprises distinct heterogeneous inflammatory disorders characterized by patients showing different phenotypes with distinct genetic components, environmental causes, and immunopathologic signa-DATA SOURCES: Ovid MEDLINE and PubMed databases from 1950 to the present time were searched for relevant articles and references regarding the heterogeneity of asthma. Study Selection: Articles that described the various phenotypes of asthma were used for this review. RESULTS: Asthma is unlikely to be a single disease but rather a series of complex, overlapping individual diseases or phenotypes, each defined by its unique interaction between genetic and environmental factors. These conditions include syndromes characterized by allergen-exacerbated, nonallergic, and aspirin-exacerbated factors along with syndromes best distinguished by their pathologic findings (eosinophilic, neutrophilic, pauci-granulocytic), response to therapy (corticosteroid resistant), and natural history (remodeling prone). Additional phenotypes will almost certainly be identified as advances in genetics and other profiling methods are made and will be accompanied by the availability of clear biomarkers for distinguishing among them. CONCLUSIONS: Responses to asthma medications vary considerably among patients, likely reflecting, at least in part, the differing sensitivities of the various asthma phenotypes. Selecting the best possible treatment course in individual patients will be aided by clearly identifying the different phenotypes. Physicians need to recognize this when making decisions to adjust treatment to improve asthma control.