Osteoarthritis (OA) involves all the structures of the joint. How the disease is initiated and what factors trigger the disease process remain unclear, although the mechanical environment seems to have a role. Our understanding of the biology of the disease has been hampered by the lack of access to tissue samples from patients with early stage disease, because clinically recognizable symptoms appear late in the osteoarthritic process. However, new data about the early processes in articular cartilage and new tools to identify the early stages of OA are providing fresh insights into the pathological sequence of events. The progressive destruction of cartilage involves degradation of matrix constituents, and rather active, yet inefficient, repair attempts. The release of fragmented molecules provides opportunities to monitor the disease process in patients, and to investigate whether these fragments are involved in propagating OA, for example, by inducing inflammation. The role of bone has not been fully elucidated, but changes in bone seem to be secondary to alterations in articular cartilage, which change the mechanical environment of the bone cells and induce them, in turn, to modulate tissue structure.