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The most frequently used drugs in human nonarthritic cartilage disease today are nonsteroidal antiinflammatory drugs, hyaluronan, and steroids. The role of these drugs in the treatment of cartilage damage, such as osteoarthritis, is unclear. Their use seems to be based on tradition, rather than on results of scientific studies. Rational drug treatment is developed on the basis of the knowledge of the pathogenetic mechanisms behind the disease. Research is increasingly advancing our knowledge of the processes involved in progressive nonarthritic cartilage disease. Investigators are currently focusing substantial work on the development of drugs that inhibit or retard the processes that are involved in cartilage matrix degradation. Preliminary results indicate that synthetic inhibitors of enzymes involved in matrix degradation in cartilage disease may open new avenues for the treatment of joint diseases.