Cardiac myocytes, although large enough to make up most of the heart volume, are only a minority of cells within the heart with fibroblasts and blood vessel components (endothelial and smooth muscle cells) making up the remainder of the heart. In recent years, there has been increasing interest in the nonmyocyte population within the heart. This is attributable, in part, to our increasing understanding of the biology of the nonmyocyte cell types and additionally it is the result of our awakening realization that these cells are not static but rather that they are dynamic in nature indicating that they play a more active role in cardiac function than previously imagined. Studies now show that fibroblasts are involved in formation of the extracellular matrix and they control the size of the extracellular matrix. Additionally, they participate in the repair process by differentiating into myofibroblasts, which are cells involved in the inflammatory response to injury. Myofibroblasts migrate to the sites of injury where they produce cytokines, thus enhancing the inflammatory response. This review discusses both structural and functional differences between the two cell types and examines the different roles of these two different cell types in the heart.