Injury to the adult mammalian central nervous system (CNS) often results in permanent loss of sensory and motor function. This is due to the failure of injured axons to regenerate. The inhibitory nature of the CNS can be attributed to several factors, including formation of the glial scar, the presence of several molecules, associated with myelin, which inhibit axonal regrowth, and the intrinsic growth state of these neurons. Encouraging regeneration in the adult mammalian CNS therefore will require targeting one or all of these factors following injury. Here we illustrate recent work from our laboratory that identifies some of the signalling components involved in modulation of the intrinsic growth state of adult neurons. When activated, these signalling pathways can induce axonal regeneration in the presence of the myelin-associated inhibitors both in vitro and in vivo.