The response to nerve injury is a complex and often poorly understood mechanism. An in-depth and current command of the relevant neuroanatomy, classifications systems, and responses to injury and regeneration are critical to current clinical success. Continued progress must be made in our current understanding of these varied physiologic mechanisms of neuro-regeneration if any significant progress in clinical treatments or outcome is to be expected in the future. Reconstructive surgeons have in many ways maximized the technical aspects of peripheral nerve repair. However, advances in functional recovery may be seen with improvements in sensory and motor rehabilitation after peripheral nerve surgery and with a combined understanding of the neurobiology and neurophysiology of nerve injury and regeneration.