In many instances, nerve biopsy is not necessary in the diagnostic work-up of a peripheral neuropathy. However, histological examination of a tissue sample is still mandatory to show specific lesions in various conditions involving peripheral nerves. As there are fewer laboratories that examine human nerve samples, practitioners including neurologists and general pathologists may not be completely aware of the technical issues and data that are provided by nerve biopsy. Nerve biopsy is considered an invasive diagnostic method, although, its complications are by far less disabling than most of the disorders that lead to its indications. Nevertheless, the decision to perform a nerve biopsy has to be made on a case-by-case basis, and its results must be discussed between the pathologist and the clinician who is in charge of the patient's care. In this paper, we review the minimal technical requirements for proper peripheral nerve tissue analysis. Moreover, we provide data on the usefulness of nerve biopsy in various situations including abnormal deposits, cell infiltrates, link between peripheral neuropathy and monoclonal gammopathy, and numerous hereditary disorders.