Despite advances in microsurgical techniques, peripheral nerve injury poses an ongoing challenge to treating surgeons. While choosing the appropriate surgical approach and using precise technique are important in obtaining optimal outcomes, current research in nerve repair focuses on using knowledge of biologic nerve regeneration to develop new strategies in peripheral nerve repair. In the following review article, the relevant anatomy and physiology involved in the regeneration of injured nerves are described. Both traditional and innovative strategies in nerve repair are discussed as well as their applicability to various nerve injuries. While the anatomy and physiology of nerves predicate their susceptibility to mechanical and ischemic injury, the specific type of injury dictates the optimal treatment algorithm. In particular, peripheral nerve injuries associated with significant gaps between damaged nerve endings provide a challenge for hand surgeons, and a variety of solutions to this problem will be discussed. Direct nerve repair continues to be the gold standard treatment for nerve lacerations. For nerve injuries that do not allow for a direct repair, alternative management options include autografts, allografts, and biologic or synthetic conduits. Recent research in neurotrophic factors present potentially groundbreaking biologic possibilities to help guide nerve regeneration after repair.