Evidence indicates that breakdown of articular cartilage resulting in the loss of normal joint function is the distinctive feature of osteoarthritis. Degradation of cartilage extracellular matrix components involves the action of at least 2 classes of proteinases: serine proteinases and metalloproteinases. Receptors have been described on a wide range of cell lines for many such proteinases [urokinase-type plasminogen activator (u-PA), plasminogen/plasmin, collagenase], which subsequently activate each other on the solid phase of the cell surface, leading to cartilage destruction. We review the leading role of u-PA and its receptor (u-PAR) in cartilage degradation.