Spinal cord injury represents a complex injury cascade; hence no single “magic bullet” will address the requirements of a therapeutic modality that could lead to functional recovery. Instead, a multimodality approach is needed to make meaningful gains in clinical treatment. In general, multimodal paradigms can be divided into those that focus on ameliorating the secondary injury cascade, and those that target remyelination and axonal and neuronal regeneration. Neuroprotection strategies have been discussed in another chapter; the focus of this article is neuroregeneration. The complicated pathophysiology of SCI makes it difficult to develop therapeutic interventions to achieve a successful neural repair; however, recent advances in areas of cell biology and biomaterials have opened up the way for new therapeutic strategies. Efforts to induce regeneration and repair of the injured cord are molecular and cell based. Molecular-based translatable therapies are directed at inhibiting myelin inhibitors, targeting intracellular messenger systems that mediate growth cone dynamics, and degrading the glial scar. Current cell-based approaches are aimed at promoting remyelination, delivering trophic molecules that can promote cellular protection and plasticity and regeneration of new neurons. Although preclinical data in experimental SCI are highly encouraging, the functional improvements are at best, modest. Further, the SCI human population is highly heterogeneous in terms of extent of injury and hence the efficacy of such treatments could potentially be highly variable among patients. There are numerous unresolved biological and ethical challenges in translating these to humans, hence at present expectations should be tempered. Cell-based transplantation strategies for the repair of SCI to date appear most successful when applied in the subacute phase of injury. The application of cell-based strategies for repair and regeneration of the chronically injured spinal cord will require a combinatorial strategy that will probably need to include approaches to overcome the effects of the glial scar, inhibitory molecules such as Rho and Nogo, and the use of tissue engineering strategies to bridge the lesion.