Tendon is a poorly vascularized and highly specialized connective tissue containing few scattered cells that play an important role in the musculoskeletal apparatus by resisting mechanical stress. Because of the slow rate of the metabolism of its molecular components, the tendon gradually loses its mechanical properties and may rupture upon an array of physical activities. In this report, we discuss the molecular changes involved in the extracellular matrix-tendon interactions leading to tissue degeneration and rupture.