Numerous factors external to the nerve cell can support and enhance nerve regeneration after injury. The definition of these factors and the elucidation of their mechanisms of action are the central goals of much contemporary neurobiologic research. This research will hopefully lead to the discovery of factors that will prove to be therapeutically beneficial for patients with either peripheral nervous system (PNS) injury or central nervous system (CNS) injury. This article reviews the biology of the regeneration response of the nerve to injury and discusses many of the factors that enhance nerve growth. Finally, the nerve guide or nerve regeneration chamber model for the evaluation of putative nerve regeneration enhancing agents in vivo is also discussed.