Peripheral neuropathy manifests as a painful syndrome in a significant number of individuals suffering from diabetes mellitus. Painful diabetic neuropathy may interfere with sleep, work, and activities of daily living. Patients and practitioners alike often view this challenging disorder as incurable. A broad spectrum of therapeutic alternatives and physiologic approaches to this complex clinical problem are available. Careful assessment and a rational approach based on the nature and location of pain will lead to success. The authors review the etiology, clinical presentation, and diagnosis of diabetic peripheral neuropathy. Available therapeutic alternatives are emphasized and an original treatment algorithm is presented.