Sympathetic damage is a striking feature of diabetic neuropathy, probably much more common and important than previously suspected. Degeneration of arterial medial smooth muscle with subsequent medial calcification is a feature of diabetic neuropathy and represents a structural abnormality probably resulting from sympathetic denervation. Loss of vasomotor control is responsible not only for postural hypotension but also for the remarkable increase of peripheral blood flow and arteriovenous shunting in the neuropathic foot. Demineralisation of bones and neuroarthropathic bone and joint destruction may result. Intractable oedema is another consequence of these haemodynamic abnormalities, while in other cases there is a close association of sympathetic defects with painful neuropathies. The possibility of new treatments using sympathomimetic agents to reverse these abnormalities now exists, and ephedrine has already been shown to be highly effective in reducing neuropathic oedema.