Cervical spondylotic myelopathy (CSM) is a very common and debilitating disease; however, its underlying pathocellular process remains uncertain. Attempts have been made to reproduce CSM in experimental animal models in order to deepen the knowledge on the molecular pathobiology of this disease. The up-to-date observations have established the apoptosis of oligodendrocytes (OLGs) as the principal pathocellular process of CSM. Since favorable neurological recovery cannot be obtained in afflicted patients, even after the decompression surgery, elucidation of the apoptotic cascade in OLGs may unveil possible molecular treatments which could inhibit demyelination and ameliorate the neurological deficits. Moreover, additional therapeutic benefits may include improvement of myelin self-repair capability by stimulating OLG progenitor cells to become mature and finally, myelinating OLGs. This review focuses on the factors and mechanisms of crucial importance for developing antiapoptotic treatments. Critical evaluations of the role of OLGs in molecular pathobiology of CSM as well as strategies for potential remyelination of CSM are also provided. The analyses and evaluations of the experimental findings can possibly lead to treatment of CSM as well as to development of novel biopharmacenticals.