Peripheral nerves are essential connections between the central nervous system and muscles, autonomic structures and sensory organs. Their injury is one of the major causes for severe and longstanding impairment in limb function. Acute peripheral nerve lesion has an important inflammatory component and is considered as ischemia-reperfusion (IR) injury. Surgical repair has been the standard of care in peripheral nerve lesion. It has reached optimal technical development but the end results still remain unpredictable and complete functional recovery is rare. Nevertheless, nerve repair is not primarily a mechanical problem and microsurgery is not the only key to success. Lately, there have been efforts to develop alternatives to nerve graft. Work has been carried out in basal lamina scaffolds, biologic and non-biologic structures in combination with neurotrophic factors and/or Schwann cells, tissues, immunosuppressive agents, growth factors, cell transplantation, principles of artificial sensory function, gene technology, gangliosides, implantation of microchips, hormones, electromagnetic fields and hyperbaric oxygenation (HBO). HBO appears to be a beneficial adjunctive treatment for surgical repair in the acute peripheral nerve lesion, when used at lower pressures and in a timely fashion (<6 hours).