Hypoglycaemia is a severe complication of insulin-dependent diabetes mellitus, especially when it is not preceded by warning signs. A patient unaware of a low blood glucose concentration may not take any remedial action, becomes severely hypoglycaemic and may lapse into a potentially fatal coma. Hypoglycaemic unawareness is associated particularly with good glycaemic control. Hypoglycaemia unawareness was first related to diabetic autonomic neuropathy. Subsequently it emerged that well controlled diabetic patients suffered from hypoglycaemia unawareness more often than poorly controlled patients. Next to autonomic neuropathy and good glycaemic control, the transfer of more slowly resorbed beef and porcine insulin to more rapidly resorbed human insulin has been incriminated as causing an increased incidence of hypoglycaemia unawareness. Reviewing the scientific literature concerning the connection between hypoglycaemia unawareness and the use of human insulin, there is no rationale for supporting the hypothesis that human insulin leads to hypoglycaemia unawareness any longer. While the pathophysiology of hypoglycemia unawareness remains unclear in patients with insulin-dependent diabetes mellitus of long duration, it may well be related to impaired adrenaline secretion. The cause of this impaired adrenaline secretion during hypoglycaemia is unknown and it does not seem to be a result of diabetic autonomic neuropathy.