There are currently no treatments available (beyond optimal control of hyperglycemia) that arrest or reverse progressive diabetic polyneuropathy. Consultation with a diabetologist is indicated for patients with poorly controlled disease and polyneuropathy. Immunotherapy for diabetic lumbosacral plexopathy has been advocated but is not supported to date by class 1 clinical trial evidence. Pharmacologic treatment for painful neuropathy may include topical anesthetics, capsaicin cream, anticonvulsants, tricyclic antidepressants, mexiletine, and opioids. Gabapentin, a newer anticonvulsant, has an attractive side-effect profile (a consideration in older patients) and has fewer interactions with other drugs. Amitriptyline may cause excessive sedation, postural hypotension, constipation, and urinary retention, but low evening doses (10 to 25 mg), slowly titrated upward, may offer relief from nocturnal pain. Opioids should not be withheld from patients with severe pain or with intolerance of or contraindications to other agents. A single physician should supervise their use.