Normal cartilage is a complex material consisting of a solid matrix composed primarily of collagen and proteoglycan, which is saturated with water. It is not a homogenous material. The interaction of the physical and biochemical structures of cartilage is necessary to allow the normal function of providing nearly frictionless motion, wear resistance, joint congruence, and transmission of load to subchondral bone. Chondrocytes are responsible for synthesizing and maintaining this material. Osteoarthritis occurs when there is disruption of normal cartilage structure and homeostasis. Osteoarthritis results from a complex interaction of biochemical and biomechanical factors that occur concurrently and serve to perpetuate degradative change. The progressive pathologic change that occurs in osteoarthritis has been characterized, not only for articular cartilage but also for periarticular tissues. The occurrence of mechanical and biochemical changes is well established, but the role of each in the etiopathogenesis of osteoarthritis is not rigidly defined. It is likely that there are multiple etiologies sharing common pathways of physical and chemical disruption. (see Fig. 1). The changes associated with osteoarthritis ultimately have an impact on the patient through decreased ability to use the joint or the production of pain, or both. Unfortunately, once these changes are severe enough to be recognized clinically, they are likely to be irreversible with current treatments. Nevertheless, understanding the basic mechanisms involved in the development and progression of osteoarthritis provides a basis for establishing a reasonable expectation for the patient and a rational plan for medical and surgical treatment of this condition.