The concept of myocardial remodeling links an initial pathological insult to a progressive geometric change of the ventricle. Currently, our concepts of the remodeling process have evolved to include not only changes in ventricular size and shape, but cellular and molecular remodeling, particularly as the ventricle evolves towards failure. In recent years, much attention has focused on the role of cell–extracellular matrix (ECM) connections in this process. In this review, we will specifically delineate how cell membrane-linked molecules of three classes: integrins, membrane-type matrix metalloproteinases, and ADAMs (A Disintegrin And Metalloproteinase) might play crucial roles in myocardial remodeling. These molecules are essential for cell–ECM adhesion, cell signaling, matrix modification, and proteolysis of surface receptors. Our goal is to put forth concepts on how they might interrelate to modulate the remodeling process in the heart.