Molecular markers of bone and cartilage metabolism are increasingly used as helpful tools in the diagnosis and early detection of joint disease. Their quantification may help to improve the ability for therapeutic monitoring and follow-up of patients affected with rheumatic or degenerative cartilage disorders. The biochemical background and the functional properties of markers of bone, cartilage, and synovial tissue turnover are described. Current clinical applications and the diagnostic and prognostic validity of these metabolites are presented with special emphasis on recent research activities. Finally, molecular aspects of bone and joint diseases are discussed, highlighting genetic contributions to the development of joint disease.