The cardiac interstitium represents a system of diverse extracellular matrix (ECM) components organized into a complex, three-dimensional network that surrounds the cellular components of the heart (Borg and Caulfield 1981, Weber et al. 1994, Comper 1995). The interaction of the cellular components with the interstitium is dynamic and occurs in response to physiological signals during development, normal homeostasis, and disease (Borg and Caulfield 1981, Weber et al 1994). Both the quantitative and qualitative expression of ECM components play an important role in cardiac function; however the mechanisms that regulate the expression and function are not well understood. The manner in which the terminally differentiated myocyte perceives its external environment is of critical importance to the function of the heart. These external signals ave delivered via the other two major components of the heart: the vascular system and the surrounding interstitium or ECM. Although it is obvious that the vascular system provides the transport of a variety of regulatory components that influence the contractile ability of the myocyte, the role of the interstitium in relation to cardiac function is less understood and is the focus of this review.