Diabetes targets the peripheral nervous system with several different patterns of damage and several mechanisms of disease. Diabetic polyneuropathy (DPN) is a common disorder involving a large proportion of diabetic patients, yet its pathophysiology is controversial. Mechanisms considered have included polyol flux, microangiopathy, oxidative stress, abnormal signaling from advanced glycation endproducts and growth factor deficiency. Although some clinical trials have demonstrated modest benefits in disease stabilization or pain therapy in DPN, robust therapy capable of reversing the disease is unavailable. In this review, general aspects of DPN and other diabetic neuropathies are examined, including a summary of recent therapeutic trials. A particular emphasis is placed on the evidence that the neurobiology of DPN reflects a unique yet common and disabling neurodegenerative disorder.