Current treatments for spinal disease are unsatisfactory, and gene therapy holds promise as a means of ensuring prolonged and consistent delivery of therapeutic proteins into the spine. Direct injection of vectors into spinal structures is limited by the current lack of vectors with a satisfactory efficacy and safety profile. Conversely, ex vivo gene transfer into cells from the spine or other tissues (bone, nervous tissue, synovial membrane) followed by re-injection of these cells into the spine seems both appropriate and feasible in patients with degenerative disk disease. Candidate genes include genes encoding interleukin-1 antagonists, tumor necrosis factor antagonists, and growth factors. Further work is in order to move gene therapy research to the clinical trial stage in patients with degenerative disk disease, thus following in the footsteps of research on rheumatoid arthritis.