In this clinical article, Dr. Rebecca Traub and Dr. Thomas Brannagan, both of Columbia University, discuss idiopathic sensory and sensorimotor neuropathies, which typically present in middle to late adulthood as length-dependent polyneuropathies with predominantly axonal features on electrodiagnostic and histologic examination. A large number of disorders cause distal polyneuropathy, and a full diagnostic evaluation must be completed before categorizing a neuropathy as idiopathic. An expanding number of conditions and risk factors are associated with neuropathy, including impaired glucose tolerance, celiac antibodies, and monoclonal gammopathies. Skin biopsy for assessment of intraepidermal nerve fiber density is a valid and reliable method of confirming the diagnosis of small fiber sensory neuropathy, but this category of polyneuropathy continues to have a high percentage of patients without known etiology. Neuropathic pain is a common presenting symptom and is often the focus of medical management; a number of antidepressants and antiepileptics have demonstrated efficacy.