Retinal ganglion cells (RGCs) and their projections in the optic nerve offer a convenient model to study survival and regeneration of mammalian central nervous system (CNS) nerve cells following injury. Possible factors affecting the death of RGCs following axotomy and various approaches to rescue the axotomized RGCs are discussed. In addition, two main strategies currently used to enhance axonal regeneration of damaged RGCs are described. The first focuses on overcoming the unfavorable extrinsic CNS environment and the second concentrates on upregulating the intrinsic growth potential of RGCs. Thus, the failure or success of RGC axonal regrowth after injury depends on the complicated interplay between the extrinsic and intrinsic factors.