The vascular extracellular matrix is a collection of vastly different macromolecules organized by entanglement and cross-linking into a biomechanically active polymer that imparts regional tensile strength, viscoelasticity, and compressibility to the atherosclerotic lesion. Each component of the extracellular matrix possesses unique structural properties that determine its separate roles during atherogenesis. Not only does this matrix provide the architectural framework that influences the structural integrity of the lesion, but it also provides the milieu for vascular cells and participates in the adhesive, proliferative, and migratory events that characterize lesion development. The fact that different components of the extracellular matrix selectively bind plasma proteins, growth factors, cytokines, and enzymes implicate these molecules in the regulation of key metabolic events in the formation of the atherosclerotic plaque. The extracellular matrix can no longer be thought of as simply an inert structural mass, but rather as a collection of molecules that possesses the capacity to 'instruct' and 'transduce the information' that 'drives' events central to the atherogenic process. A more thorough understanding of the nature and properties of the vascular extracellular matrix and the factors that regulate its accumulation would seem to be a reasonable goal if progress is to be made towards alleviating this disease.