Recent biologic and biochemical advances have furthered our understanding of the complex environment of the intervertebral disk. This new understanding has allowed researchers to pursue novel treatments of intervertebral disk degeneration, targeting the biochemical pathways involved in the degenerative cascade. Gene therapy has shown much promise in this regard. Many new targets for gene therapy in the intervertebral disk have been identified, such as TGF-β1, TIMP-1, and LMP-1. In addition, new vectors, such as the adeno-associated virus, are being investigated for use in intervertebral disk applications. Cell-based therapy has also shown significant promise in the biologic treatment of intervertebral disk degeneration. With continued efforts, gene therapy may prove to be an extremely powerful tool in the treatment of intervertebral disk degeneration.