Spinal cord injury (SCI) is a major medical problem, because there currently is no way to repair the central nervous system (CNS) and restore its function. This chapter focuses on embryonic stem (ES) cells as an important research tool and potential therapy. It reviews the epidemiology, functional anatomy, and pathophysiology of SCI, and describes spontaneous regeneration and limitations on repair. There are four to five times as many spinal cord injuries caused by medical conditions as well, such as multiple sclerosis, a common disorder that destroys the myelin insulation on nerves in the cervical spinal cord. Unlike the brain, the spinal cord has its white matter on the outside and gray matter on the inside. The outer white matter also contains astrocytes and blood vessels, but it consists mostly of axons and oligodendrocytes glial cells that wrap axons in white, insulated myelin. Evidence suggests that factors in the CNS actively inhibit regeneration; such factors include inhibitory proteins in the cord, which guide regrowing connections, and scar tissue, which contains chondroitin sulfate and proteoglycans. Reduced production of growth factors that stimulate regrowth also limits regeneration. To understand spinal cord regeneration, it is necessary to understand spinal cord development. Transplantation of genetically modified cells contributes to repair and recovery from spinal injury.