Neuropathy is one of common manifestations of diabetes mellitus (DM) and it increases in incidence and severity as DM progresses, in particular if not well controlled. Neuropathy affects all nerve fiber types and in individual patients manifests with different severity leading to a range of symptoms from painless loss of sensation to severe pain or combination of both. The foundation of control of neuropathy and associated pain is blood sugar control and disease management. Influence of other metabolic and hormonal factors is now recognized as ones that could contribute to progression of neuropathy. In addition to disease management, pharmacotherapy is an important component of treatment for diabetic neuropathy (DN), in particular for painful. Number of therapies for DN is very limited and effects are small and not easy to reproduce. In contrast a few therapies have been investigated and a couple of them, pregabalin and duloxetine, are approved for treatment of pain in DN. Recent studies point to the fact that combination therapy is more effective than individual drugs. Certainly this approach needs to be weighed against side effects of the combination.