Gene therapy has now reached the clinic for several neurological disorders, including spinal muscular atrophy (SMA), retinitis pigmentosa, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and leukodystrophies. These remarkable advances have demonstrated feasibility, relative safety, and efficacy of gene therapy approaches for treating disorders of the brain and spinal cord and add momentum to the development of gene therapies for spinal cord injury, where they hold great potential. This review provides an overview of the application of gene therapy in pre-clinical experimental models for spinal cord injury and gives a perspective on the path to clinical translation. We start with a historical overview of viral vector types and modes of viral vector delivery that have been applied to deliver therapeutic genetic material to the injured spinal cord. Subsequent sections of this review highlight the use of gene therapy approaches to target multiple aspects of the complex nature of spinal cord injury pathophysiology, including enhancing neurotrophic support, modifying the extracellular matrix and the immune response, and activating the neuron-intrinsic response to injury. Finally, we highlight future directions in spinal cord gene therapy research and a clinical outlook.