This chapter provides detail description of Pathophysiology of disc degeneration. Introduction of intervertebral disc, anatomy of intervertebral disc, nucleus pulposus, annulus fibrosus, physiology of intervertebral disc, nutrition and metabolism of intervertebral disc, biomechanics, age changes in intervertebral disc, degenerative disc disease, aetiology of degenerative disc disease, disc regeneration, clinical correlation, imaging correlations, gene therapy and cell based therapy are described in detail. 81 references are included at the end of the chapter to facilitate further reading