Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that cannot be specified otherwise. However, surgical removal of a piece of nerve causes a sensory deficit and–in some cases–chronic pain. Therefore, a nerve biopsy is usually performed only when other clinical, laboratory and electrophysiological methods have failed to clarify the cause of disease. The neuropathological work-up should include at least paraffin and resin semithin histology using a panel of conventional and immunohistochemical stains. Cryostat section staining, teased fiber preparations, electron microscopy and molecular genetic analyses are potentially useful additional methods in a subset of cases. Being performed, processed and read by experienced physicians and technicians nerve biopsies can provide important information relevant for clinical management.