In the last decade, numerous studies have emphasized the important functions that matricellular proteins subserve during angiogenesis, wound healing, and the maintenance of organ and tissue integrity. Matricellular proteins are defined as a group of secreted regulatory macromolecules that are not structural components of the extracellular matrix (ECM) but rather mediate interactions between the ECM and cells. One of these matricellular proteins, termed SPARC (secreted protein acidic and rich in cysteine), is produced during the process of wound healing and is prominent in several types of injury. An excessive deposition of glomerular matrix and an elevated proliferation of certain glomerular cells characterize a variety of kidney diseases. The proliferation of these cells is associated typically with the remodeling process that occurs after kidney injury, and is, at least in part, modulated by the altered expression of ECM, various growth factors, and the elevated production of matricellular proteins (e.g., SPARC). The secretion of one or more of the matricellular proteins can lead to expansion of the glomerular basement membrane, infiltration of immunocompetent cells, and, in some cases, to a reversal of the pathological condition. However, these proteins can also contribute collectively to renal fibrosis, glomerulosclerosis, glomerulonephritis, and the eventual loss of renal function. The purpose of this review is to evaluate the multiple functions of SPARC in the kidney glomerulus under normal and pathological conditions.