Painful diabetic neuropathy is a common distressing and challenging condition. The mechanism or mechanisms involved in its pathogenesis continue to elude clinical scientists. As with other conditions of painful distal symmetrical neuropathic conditions, pain relief involves the use of a variety of analgesic and neuroleptic drugs, aimed at reducing either central responses to painful stimuli or at dampening spontaneous irritability of affected neurons. More recently, several therapies directed at putative pathologic mechanisms specific to painful diabetic neuropathy have evolved. These include vasodilators, protein kinase C beta inhibition, antioxidants, and novel aldose reductase inhibitors. Preliminary clinical studies of these therapies have at present involved small numbers of patients; however, the results have been encouraging. This article considers the clinical aspects of diagnosis and management of chronic painful diabetic neuropathy, focusing on existing and newer therapies.