Abstract: Diabetic neuropathy (DN) is a common complication of both type-1 and type-2 diabetes, which affects over 90% of the diabetic patients. The distal symmetrical polyneuropathy (DSPN) is the commonest clinical form of diabetic neuropathy, affecting more than 90% of the patients. Painful diabetic neuropathy (PDN) is one of the most common of all type of the long-term complication of diabetes, affecting up to 50% of patients. The most common sites of pain are in the periphery involving the feet, toes, and hands. DNP continues to represent a therapeutic challenge as its pathophysiology is not yet fully understood and pain relief is still unsatisfactory. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. This review does not widely discuss all possible treatments for painful neuropathy; however it provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient.