Asthma is a common disorder of the airways which exhibit variable obstruction associated with hyperresponsiveness linked to altered smooth muscle. Although environmental factors are important in the origins and progression of asthma, it is a disorder with high heritability. The identification of ADAM33 (ADAM metallopeptidase domain 33, a disintegrin and metalloproteinase domain 33) as the first novel asthma gene has implications for the mechanisms of airway hyper-responsiveness and airway wall remodeling. This review discusses the molecular regulation of ADAM33, its link to asthma and chronic obstructive pulmonary disease and newly identified functions. These all point to ADAM33 being a key molecule in the development and progression of asthma by contributing to smooth muscle and vascular modeling and remodeling. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.