Antihypertensive treatment in diabetes mellitus, especially in diabetics known to have cardiac autonomic neuropathy, may have to consider the status of the autonomic nervous system. In diabetic subjects with cardiac autonomic neuropathy, vagal activity during the night is often reduced. The reduction results in relative or absolute sympathetic activation, which could increase cardiovascular risk. Pathophysiological and clinical data suggests that antihypertensive treatment should reduce rather than induce sympathetic activity in this setting. Beta blocking agents, ACE inhibitors, calcium antagonists of verapamil or diltiazem type and selective imidazoline receptor agonists reduce sympathetic activity and, therefore, may have a beneficial effect in diabetic patients with disturbed sympathovagal balance.