The telomeric region of repetitive DNA sequences at the end of chromosomes prevents end-to-end fusion of chromosome terminals and deterioration of the doublestrand free ends. Because of the ‘end-replication problem’, telomeres shorten with each round of cell division, resulting in cell senescence. The enzyme telomerase compensates for telomere shortening by elongating telomeric sequences, thereby prolonging the lifespan of the cell. Studies of articular cartilage and bone tissues have indicated that telomere shortening limits normal cell function and proliferation, while the telomere maintenance mechanisms of osteosarcoma cells facilitate escape from cell death and promote immortality. This article reviews the literature on this topic and provides an extensive discussion of the basic molecular biology and roles of telomeres and telomerase in musculoskeletal diseases such as osteoarthritis, osteoporosis and osteosarcoma. Findings to date suggest that telomeres and telomerase may become novel therapeutic targets for the diagnosis, treatment and prevention of musculoskeletal disorders.