Low back pain due to disc degeneration is one of the largest health problems faced in this nation when judged by lost work time and direct as well as indirect costs. Many experimental methods are being explored to treat or to reverse the effect of disc degeneration. This article reviews the strategy of a tissue engineering approach to disc regeneration. Mesenchymal stem cells (MSC) such as those obtained from marrow stroma when exposed to the appropriate microenvironment (hypoxia, growth factor, three dimensional culture) differentiate into nucleus pulposus-like cells. These then may be candidates for transplantation and nucleus repopulation. While the work is in its infancy, there is significant optimism that next steps will lead to organ culture models of disc degeneration and regeneration, and ultimately to in vivo rescue of degenerating discs with stem cell treatment.