Chronic inflammation in vascular disease affects the organization of the extracellular matrix (ECM) in such a way as to promote the events associated with atherosclerosis and restenosis. Versican and hyaluronan are two ECM components that are affected by inflammation and, in turn, affect the inflammatory response. Inflammatory growth factors such as TGF-β1 and PDGF stimulate the production of versican and hyaluronan by arterial smooth muscle cells (ASMCs). These ECM components accumulate in vascular disease and promote the proliferation and migration of ASMCs, contributing to intimal hyperplasia. Hyaluronan also serves as attachment ligand for inflammatory cells and may be partly responsible for leukocyte retention as part of the early inflammatory response. Inflammation also leads to destruction of the ECM and failure of the ECM to remodel. Elastic fibers are absent in atherosclerotic and restenotic lesions and controlled expression of a versican variant, V3, in ASMCs restores the ability of these cells to form elastic fibers. ECM assembly is critical to vascular healing and the prevention of vascular disease.