This review has presented the arguments for administration of replacement T3 and T4 hormone in patients with NTIS. However, it is impossible to be certain at this time that it is beneficial to replace hormone, or whether this could be harmful. Only a prospective study will be adequate to prove this point, and probably this would need to involve hundreds of patients. One cannot envisage that replacement of thyroxin or T3 can "cure" patients with NTIS. The probable effect, if any is achieved, will be a modest increment in overall physiologic function and decrease in mortality. Perhaps this would be 5%, 10%, or 20%. If effective, thyroid hormone replacement will be one of many beneficial treatments given the patient, rather than a single magic bullet which would reverse all the metabolic changes going wrong in these severely ill patients. Ongoing studies document the beneficial effects of hormone replacement in these acutely and severely ill patients. Possibly therapy will ultimately involve replacement of peripheral hormones, or may instead be via GHRP, TRH, GNRH, insulin, adrenal steroids, and leptin.