Ossification of the posterior longitudinal ligament of the spine (OPLL) is an ectopic ossification in spinal ligament tissues and its progression results in serious neurological deficiencies. Although the etiology of OPLL has been extensively investigated from various standpoints, the detailed mechanism of development has not been clarified. As an established therapy, surgical treatment is generally applied to the patients and has brought about considerable success. However, it is often associated with a higher risk of reprogression of ossification followed by neurological complications. Therefore, advances in safe and effective therapy to prevent the progress of OPLL have been required. In this review the possible mechanisms of ectopic ossification in spinal ligament tissues and pharmacological view of medical treatment of this disease are discussed.