This chapter discusses pathophysiology of spinal cord injury and strategies for repair. Spinal cord injury initiates an immune response characterized in part by the synthesis of cytokines and chemokines and a coordinated infiltration of the damaged site by peripheral leukocytes. The SCI site contains large numbers of both apoptotic and necrotic neurons and glia. Vascular events of secondary injury include the disruption of the blood-spinal cord barrier (BSB) that is closely associated with edema formation. Potential treatment modalities can be broadly divided into five Categories; (1) Neuroprotection, to prevent death of neural cells undamaged by the initial injury; (2) Stimulating axonal growth, either by enhancing the intrinsic regenerative capacity of neurons or by blocking or removing endogenous inhibitors to repair; (3) Bridging, to provide a permissive substrate for elongating axons and to replace lost tissue; (4) Enhancing axonal transmission, to alleviate conduction block in spared or regenerated axons and (5) Rehabilitation, to enhance functional plasticity within circuits and consolidate anatomical repair.