Regenerating axons stop growing when they reach the border of the glial-fibrotic scar, presumably because they encounter a potent molecular barrier inhibiting growth cone advance. Chemorepulsive axon guidance molecules provide a non-permissive environment restricting and channeling axon growth in the developing nervous system. These molecules could also act as growth-inhibitory molecules in the regenerating nervous system. The receptors for repulsive guidance cues are expressed in the mature nervous system, suggesting that adult neurons are sensitive to the activity of developmentally active repulsive proteins. In this review, we summarize recent observations on semaphorins, ephrins, and slits in the injured brain and spinal cord, providing evidence that these proteins are major players in inhibiting axonal regeneration and establishing the glial-fibrotic scar.