Meticulous metabolic management of diabetes has become a feasible therapeutic option now being offered to increasing numbers of diabetics in the hope of delaying or preventing diabetic complications. This hope, while still untested by rigorous clinical trials, is nevertheless supported by a considerable body of scientific and clinical data (see ref. 1 for a review) and could well represent the first truly significant therapeutic advance since the discovery of insulin. Recently, however, several reports of unexpected deaths have occurred in patients “tightly” controlled with open-loop insulin delivery devices. At least some of these deaths are believed to have been directly or indirectly attributable to hypoglycemia. These reports, together with new understanding of the hormonal and metabolic lesions in treated and untreated type I diabetes, have raised legitimate questions as to the safety of efforts to normalize glycemia, whether by continuous subcutaneous insulin infusion or by multiple injections. In this review, the potential long-term benefits of meticulous glucoregulation will be weighed against the short-term risks, particularly the risk of hypoglycemic brain damage, and guidelines will be proposed in the hope of reducing the risk-benefit ratio of such regimens to an absolute minimum.