Axonal damage and degeneration are prominent components of acute neurological disorders such as stroke, brain and spinal cord injuries, leading to the dysfunction of neuronal networks, which is largely responsible for the impaired neurological function. In the CNS, injured axons not only degenerate but are unable to regenerate and have a limited capacity to sprout and re-establish lost connections. Therefore, axonal damage often results in long term disability. Strategies aimed at fostering neurological recovery by promoting axonal sprouting and regeneration have largely targeted the glial inhibitory environment that develops following central nervous system injury. However, experimental evidence suggests that providing a favorable environment may not be the sole and sufficient means for functional regeneration, and that activating the limited intrinsic potential of neurons to sprout and regenerate may represent an alternative and complementary therapeutic approach. Experimental data that show how the modulation of the intrinsic potential of neurons can promote axonal sprouting and regeneration in the CNS are presented and discussed. These data may suggest future therapeutic opportunities to promote recovery in acute neurological disorders.