Major peripheral nerve injuries in the upper extremities can result in significant morbidity. Understanding the pathophysiology of these injuries aids in the assessment and planning of appropriate treatment. With limited nerve mobilization, tension-free repairs can often be performed using sutures, fibrin glue, or nerve connectors. Acellular allograft and autograft reconstruction are better for bridging any gaps greater than a few millimeters. Adherence to proper principles of nerve repair improves the chances of achieving a favorable result, although in general these injuries portend a guarded prognosis.