The natural ability of the adult central nervous system of higher vertebrates to recover from injury is highly limited. This limitation is most likely due to an inhospitable environment and/or intrinsic incapacities of the neurons to re-extend their neurites after injury or axotomy. The rat corticospinal tract is the largest tract leading from brain to spinal cord and is often used as a model in developmental and regeneration studies. The extensive know-how of factors involved in the development of the corticospinal tract did provide the foundation for many studies on corticospinal tract regrowth after injury in the adult spinal cord. The results of these experiments, as discussed in this review, have led to important contributions to the further understanding of central nervous system regeneration.