Molecules that are found in the extracellular environment at a CNS lesion site, or that are associated with myelin, inhibit axon growth. In addition, neuronal changes--such as an age-dependent reduction in concentrations of cyclic AMP--render the neuron less able to respond to axotomy by a rapid, forward, actin-dependent movement. An alternative mechanism, based on the protrusive forces generated by microtubule elongation or the anterograde transport of cytoskeletal elements, may underlie a slower form of axon elongation that happens during regeneration in the mature CNS. Therapeutic approaches that restore the extracellular CNS environment or the neuron's characteristics back to a more embryonic state increase axon regeneration and improve functional recovery after injury. These advances in the understanding of regeneration in the CNS have major implications for neurorehabilitation and for the use of axonal regeneration as a therapeutic approach to disorders of the CNS such as spinal-cord injury.