Asthma is a disease characterized by marked structural changes within the airway wall. These changes include deposition of extracellular matrix proteins and an increase in the numbers of airway smooth muscle cells and subepithelial fibroblasts. Both these cell types possess properties that would enable them to be involved in remodeling and inflammation. These properties include the production of a variety of cytokines; growth factors and fibrogenic mediators; proliferation, migration and release of extracellular matrix proteins; matrix metalloproteinases; and their tissue inhibitors. Airway smooth muscle and subepithelial fibroblasts are likely to be key players in the asthmatic airway pathophysiology through their interaction with each other, inflammatory cells, and other mesenchymal cells, such as the epithelium. Current asthma therapies lack the ability to completely prevent or reverse the remodeling of the airways, therefore indicating the need for new therapeutic strategies to counter this important aspect of asthma.