T he extracellular space, or the interstitium, can be broadly divided into a fluid phase (water, electrolytes, nutrients, and some plasma proteins) and the extracellular matrix (ECM). In the heart, the ECM comprises structural proteins (primarily collagen types I and III) that form the fibrillar structure of the matrix; the basement membrane that forms an interface between the cardiomyocytes and the interstitial space as well as the molecules that mediate the cell-ECM connection; and the nonstructural proteins such as proteoglycans. Molecules traveling in the extracellular space come in contact with different ECM components, and these interactions determine the direction, speed, and distance of their transport, whereas the ECM can also provide a reservoir for several growth factors and cytokines. Moreover, the cell-ECM connection allows for transmission of signals across the cell membrane. Therefore, in addition to the classical role of ECM in providing structural support, it contributes to a multitude of intra-and extracellular events. Several thorough reviews have been published recently on the structural properties of the ECM and its remodeling in heart disease. [1][2][3] In this review, we will discuss less explored aspects of ECM function, such as its conductivity in extracellular transportation, its role in cell-cell interactions, and different modes of cell-cell communication through the extracellular space.