This article reviews the etiology and pathogenesis of osteoarthritis, particularly one of several current concepts concerning the possible central mechanisms regulating degradation of cartilage. According to this theory, degradation involves diffuse or focal exposure of the extracellular matrix to active neutral metalloproteinases, which then results in injury as well as initiation of repair processes. Diffuse matrix exposure is probably not a physiologic aberrancy but rather a pathologic result of either physical injury to local chondrocytes or inflammatory mediators.