THE CENTRAL NERVOUS SYSTEM (CNS) is incapable of meaningful regeneration of lost neurons or axonal and dendritic connections after injury. This often results in permanent and severe loss of neurological function. The CNS regenerative process is unsuccessful for at least three reasons: neurons are highly susceptible to death after CNS injury; the CNS extracellular milieu contains multiple inhibitory factors that make it nonpermissive to growth; and the intrinsic growth capacity of postmitotic neurons is constitutively reduced. However, a number of recent developments in each of these areas is providing insight into the cellular mechanisms involved in CNS regeneration and may eventually lead to the development of therapies capable of effecting successful CNS regeneration.