The primary agents responsible for cartilage and bone destruction in joint diseases are active proteinases degrading collagen and proteoglycan. All four main classes of proteolytic enzymes are involved in either the normal turnover of connective tissue or its pathological destruction. These proteinases are made by different cells found within the joints. Both extracellular and intracellular pathways exist and individual enzymes can be inhibited by specific proteinaceous inhibitors that block their activity. Recent research has implicated the matrix metalloproteinases (MMPs) in many of the processes involved in joint diseases. Conventional treatments do little to affect the underlying disease processes and recently the use of proteinase inhibitors has been suggested as a new therapeutic approach. Inhibitors of proteinases can prevent the destruction of animal cartilage in model systems and future patient trials will test the effectiveness of these compounds in vivo.