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The human cartilage and bone is characterized by a remodeling during the life, well balanced by neosynthesis and degradation of matrix components. In different joint diseases, it becomes imbalanced and the destruction of the cartilage supersedes the repair. In tissue processes in disease and in normal turnover of the matrix, these molecules are fragmented and released into surrounding fluids, in the synovial fluid, and then in the blood and the urine, where they can be detected. The quantitative measurement in the synovial fluid is more specific than in the other body fluids. The research process in recent years has suggested that these molecular markers of cartilage and bone matrix metabolism can be used to determine diagnosis, the disease severity rather than its presence or absence, the prognosis, and the response to therapy. They should help to identify the disease mechanism in different joint diseases not only on the tissue but also on the molecular level. The specific cartilage matrix markers promise to become useful tools in the future in clinical use. The research in this area is still in the early stages, with most results dated from the end of the 1980s and the 1990s.