Over the past 2 decades, the biological understanding of the mechanisms underlying structural and functional repair of the injured central nervous system has strongly increased. This has resulted in the development of multiple experimental treatment strategies with the collective aim of enhancing and surpassing the limited spontaneous recovery occurring in animal models and ultimately humans suffering from spinal cord or brain injuries. Several of these experimental treatments have revealed beneficial effects in animal models of spinal cord injury. With the exception of neurorehabilitative therapies, however, therapeutic interventions that enhance recovery are currently absent within the clinical realm of spinal cord injury. The present review surveys the prospects and challenges in experimental and clinical spinal cord repair. Major shortcomings in experimental research center on the difficulty of closely modeling human traumatic spinal cord injury in animals, the small number of investigations done on cervical spinal injury and tetraplegia, and the differences in lesion models, species, and functional outcome parameters used between laboratories. The main challenges in the clinical field of spinal cord repair are associated with the standardization and sensitivity of functional outcome measures, the definition of the inclusion/exclusion criteria for patient recruitment in trials, and the accuracy and reliability of an early diagnosis to predict subsequent neurological outcome. Research and clinical networks were recently created with the goal of optimizing animal studies and human trials. Promising clinical trials are currently in progress. The time has come to translate the biologic-mechanistic knowledge from basic science into efficacious treatments able to improve the conditions of humans suffering from spinal cord injury.