The ossification of ligamentum flavum (OLF) is a major cause of thoracic spinal stenosis. Due to insidious onset, OLF usually results in severe compression of spinal cord when discovered, and the clinical outcomes are poor. Therefore, novel and effective diagnostic and therapeutic approaches for OLF are greatly needed. Bone morphogenetic protein 2 (BMP-2), a member of the transforming growth factor β family, possesses a critical role in the differentiation of mesenchymal stem cells towards osteoblastic lineage and endochondral ossification in the early stage of embryonic development. Increasing researches revealed that OLF, especially the continuous multilevel ossification, correlates closely with BMP-2. In this review, we summarized the advances on the role of BMP-2 in the occurrence and development of OLF, and prospected the application of BMP-2 as a potential target in the diagnosis, therapy and prognosis monitoring of OLF.