INTRODUCTION Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available. AREAS COVERED The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005-2015). EXPERT OPINION The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified T-type voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channels, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.