Recent advances in understanding the pain associated with diabetic neuropathy are likely to provide significant mechanistic insights and offer better therapies. In clinical research, new tools for measuring neuropathic pain and validation of histologic and other biomarkers will provide the foundation for research advances, and new clinical trial designs will allow better discrimination of beneficial treatments and may reveal underlying pathogenic mechanisms. Ongoing refinement of relevant animal models and assays to more accurately reflect the clinical condition will improve evaluation of novel pharmacologic approaches while dissecting peripheral versus central effects of diabetes on pain pathways will provide a more complete picture of the pathophysiologic mechanisms. Such multidisciplinary work may soon allow physicians to offer improved therapeutic options to patients suffering this distressing condition.