The trabecular meshwork is one of the primary tissues of interest in the normal regulation and dysregulation of intraocular pressure (IOP) that is a causative risk factor for primary open-angle glaucoma. Matricellular proteins generally function to allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). In non-ocular tissues, matricellular proteins generally increase fibrosis. Since ECM turnover is very important to the outflow facility, matricellular proteins may have a significant role in the regulation of IOP. The formalized study of matricellular proteins in trabecular meshwork is in its infancy. SPARC, thrombospondins-1 and -2, and tenascins-C and -X, and osteopontin have been localized to varying areas within the trabecular meshwork. Preliminary evidence indicates that SPARC and thrombospondin-1 play a role in the regulation of IOP and possibly the pathophysiology of glaucoma. These data show promise that matricellular proteins are involved in IOP dysregulation and are potential therapeutic targets. Further study is needed to clarify these roles.