The factors inhibiting regeneration in the central nervous system (CNS) have been elaborated, debated, and studied for the past 70 years. Recent work has pointed to the fine balance that exists between repair and regeneration following CNS injury. Growth factors have featured prominently in this debate. In attempts to tip the scales toward regeneration and functional reconnection to damaged neurons, pharmacological intervention has come to the fore. However, a perennial concern has been that much of regeneration may be aberrant, although there is now evidence to suggest that this fear may have been exaggerated. In searching for additional avenues for achieving therapeutic reconstruction of damaged neural pathways, transplantation studies occupy a prominent place in the literature. Various principles have become established, and these have proved relevant for all approaches utilizing grafts. Xenotransplantation and stem cell transplantation are approaches with exciting potential. Circuitry can be effectively restored by xenotransplantation, including early indications of integration of pig dopaminergic neurons in Parkinson's disease. The considerable possibilities offered by the differentiation of neural stem cells into progenitor cells and then into neurons and glia are explored.