Clinical examination and electrodiagnostic studies remain the gold standard for diagnosis of nerve injuries. Diagnosis of chronic nerve compression (CNC) injuries may be difficult in patients with confounding factors such as diabetes. The treatment of nerve entrapment ranges from medical to surgical management depending on the nerve involved and on the severity and duration of compression. Considerable insights have been made at the molecular level differentiating between nerve crush injuries and CNC injuries. While the myelin changes after CNC injury were previously thought to be a mild form of Wallerian degeneration, recent evidence points to a distinct pathophysiology involving Schwann cell mechano-sensitivity. Future areas of research include the use of Schwann cell transplantation in the treatment regimen, the correlation between demyelination and the onset of pain, and the role of Schwann cell integrins in transducing the mechanical forces involved in nerve compression injuries to Schwann cells.