Cells attach to proteoglycans and glycoproteins on the surface of other cells as well as in the extracellular matrix (ECM) substratum via adhesion molecules to define tissue shape, structure, and function. Making and breaking cellular contacts with other cells and the ECM play critical roles in normal processes such as cell growth, division, differentiation, and migration. Cardiovascular and central nervous system disorders and pathophysiological processes such as fibrosis and inflammation require ECM remodeling. Remodeling involves expression of different cell adhesion molecules, altering cellular processes such as migration and polarity. Key ECM proteins include fibronectin, laminin, and collagens as well as metalloproteinases that remodel the ECM. Important cell adhesion genes include integrins, selectins, celladhesion molecule family members (ICAM, ECAM, NCAM, PECAM, and VCAM), and the catenins which link cell adhesion molecules and the cytoskeleton. Analysis of these essential genes may identify novel mechanisms in ECM remodeling and dysregulation.