The management of diabetic panful neuropathy has moved from empirism to evidence-based medicine. However appropriately targeting current medications, and the successful clinical development of drugs acting on new targets remain challenging: innovative approaches  to  improving therapeutic strategies are required. These mainly encompass rational combination therapy (eg OPTION study), drug repurposing (eg NMDA antagonists, botulinum toxin A), non-pharmacological approaches such as neurostimulation techniques (eg rTMS) and personalized therapeutic management. We will discuss current perspectives regarding the management of painful diabetic neuropathy and explore potential avenues for future research.