Atherosclerosis is primarily a lesion that progresses due to a series of reactions that are induced by repair of injured intima. The intercellular networking that occurs among smooth muscle cells, macrophages, T lymphocytes and endothelial cells leads to a fibroproliferative response, in which the extracellular matrix (ECM) plays an important role. The ECM, composed of a mixture of vastly different macromolecules including collagen, elastin, glycoproteins and proteoglycans, confers tensile strength and viscoelasticity to the arterial wall. Each component of the ECM possesses unique structural properties that determine its own roles during the development of atherosclerotic plaques. Not only does the ECM provide the structural integrity of the plaques, but it also participates in several key events such as cell migration and proliferation, lipoprotein retention and thrombosis. The various matrix metalloproteinases (MMPs), major enzymes in ECM degradation, and their inhibitors (tissue inhibitors of MMPs) are demonstrated in plaque. An excess of MMPs over inhibitors contributes significantly to ECM destruction rendering the plaque more prone to rupture. Accumulating information on the molecular regulation of ECM synthesis and degradation will help investigators attain a more thorough understanding of the mechanisms of plaque formation and plaque instability and rupture.