Osteoarthritis is a disease in which most or all of the joint structures are affected by pathology. The defining tissue affected is the thin layer of hyaline articular cartilage interposed between the two articulating bones. This avascular tissue becomes worn away, especially in areas of injury. There is also degeneration of fibrocartilaginous structures like the meniscus, sclerosis of underlying bone, growth of osteophytes at the joint margin, weakness and atrophy of muscles that bridge the joint, ligamentous laxity and disruption and, in many joints, synovitis. With focal cartilage loss on one side of the joint and bony remodeling there, malalignment across the joint can develop, increasing focal transarticular loading and causing further damage to cartilage and underlying bone. Both subtle chronic and flagrant acute injuries can start this disease process. Cartilage matrix turnover, spurred by daily loading across the joint, can replenish cartilage, but as a consequence of genetic abnormalities, age, and other metabolic factors not yet fully understood, some cartilage is especially vulnerable to loading that for normal cartilage, may be well tolerated.