Once thought to be rigidly wired, the spinal cord now is understood to display significant plastic properties, which are manifest as both physiological and structural alterations in response to changes in patterns of use, disuse, and damage. Activity-dependent increases in responsiveness of spinal cord circuits are now thought to underlie or contribute importantly to the hyperalgesia that often follows neurological injuries, the physical therapy-induced improvement in walking and running seen in patients with stroke and spinal cord injury, skill acquisition in normal children, and several other phenomena. Physiological mechanisms underlying spinal cord plasticity include denervation supersensitivity, long-term potentiation, long-term depression, and habituation. Anatomical plasticity seen in the spinal cord after partial injuries includes collateral sprouting of spared axons in response to injury of neighboring axons, and dendritic remodeling in response to loss of regionally segregated synaptic inputs. A form of neuroplasticity that is seen in the peripheral nerves and in the spinal cord of some cold-blooded animals, but not in the central nervous system of birds or mammals, is axon regeneration. It is often difficult to distinguish between regeneration of injured axons and collateral sprouting of neighboring uninjured axons, but the distinction could be very important, especially in the case of complete spinal cord injuries. Several instances of treatment-induced axonal changes that were originally thought to indicate regeneration have turned out to be collateral sprouting. There is reason to suspect that the molecular mechanisms that underlie these two phenomena are different, and, if so, therapeutic approaches to enhancing them may also prove to be very different.