Intervertebral disc (IVD) degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to degeneration of the disc and surrounding area. Degeneration of the disc is considered to be a normal process of aging, but can accelerate faster than expected or be precipitated by other factors. The scientific community has come a long way in understanding the biological basis and interpreting the lifestyle implications of IVD degeneration. Of all the diseases of the intervertebral disc, degeneration is the most common and has earned much attention due to its diversity in presentation and potential multiorgan involvement. We will provide a brief overview of the anatomic, cellular, and molecular structure of the IVD, and delve into the cellular and molecular pathophysiology surrounding IVD degeneration. We will then highlight some of the newest developments in stem cell, protein, and genetic therapy for IVD degeneration.