Generally, the axons in the adult mammalian central nervous system (CNS) do not regenerate after injuries. This lack of regeneration results in partial disability or complete paralysis. To date, several axon growth inhibitors that are known to inhibit axon regeneration in the CNS have been identified in the myelin. Recent research has revealed the molecular mechanisms underlying the action of these inhibitors. RhoA and Rho-kinase--a downstream effector of RhoA--are key signals that elicit axon inhibition. These findings provide a number of promising strategies to promote axon regeneration after CNS injuries. Some strategies such as Rho/Rho-kinase inhibition have proved effective in animal models. Elucidation of the complete mechanism of the signal transduction will be useful for the development of efficient therapeutic strategies against injuries of the CNS.