The role of intensive insulin therapy in the Medical ICU remains unclear as recent clinical trials have not been able to show a benefit as easily as they were able to do in the Surgical ICU setting. This study attempts to address that issue in a specific subset of critically ill patients, those with septic shock. Critically ill patients with septic shock are now commonly treated with corticosteroids (which raises another debate as to whether the evidence supports this practice) thus they frequently have sugars higher than 180 mg/dL, the level recommended by the guidelines at which insulin therapy should be initiated. This study is thus timely, albeit small, with only 509 randomized subjects. The primary outcome was inhospital mortality (or 90-day mortality, whichever occurred first). The standard care group actually maintained a sugar around 150 while the intensively treated group remained above target, at about 120. Although the prespecified target to reach significance appears to be overly ambitious, the final result actually showed almost no difference between the two groups (122 vs 188 deaths). The additional arm testing addition of fludrocortisone (a therapy “recommended” by guidelines in these patients) also showed no benefit. The question now becomes whether insulin has no benefit in the setting of septic shock or has standard care improved so much, because the practitioners have learned from the prior studies (as evidenced by the sugars of 150 in that group), that such trials will need to be performed on a much larger scale in the future to show any significant benefit? It is very possible that the latter will be the case, which will require a very large, multi-center international consortium to coordinate the trials. Kittie Wyne, MD, PhD, FACE