The auditory nerve is an important target in hearing restoration research along with the hair cells. Although there are several potentially useful therapeutic options to rebuild lost hearing, cell transplantation is a very realistic option. Cells can be infused into the auditory nerve without compromising the auditory brainstem responses and damaging the membranous labyrinth. The final fate of transplanted cells may be determined by the intrinsic molecular program and the extracellular guidance cues. The first factor may be largely decided by the type of donor cell used and the second factor can be modified by the application of various molecules. Our recent experiments using ontogenetic-stage/region-restricted precursors and embryonic stem cells suggest that donor cells at later development stages seemed to have more mature intrinsic molecular programs to guide them more precisely and efficiently to the final expected destination. We discuss the critical interactions between the extracellular molecules such as myelin-derived inhibitory molecules expressed after CNS injury and the intracellular actin dynamics regulated by Rho GTPases in relation to the regeneration of the auditory neurons.