A 33-year-old woman experienced 90 min of in-hospital cardiac arrest following an intentional overdose of anhydrous caffeine powder. In the face of prolonged and apparently futile resuscitation attempts, high-dose insulin euglycemic therapy was initiated. A loading dose of 1 IU/kg/h of IV insulin resulted in a dramatic improvement in perfusion. This was augmented by a 72-h infusion reaching a maximal rate of 10 IU/kg/h. The patient recovered full neurologic function and survived to discharge. Although high-dose insulin is effective in beta-blocker, calcium channel blocker, and tricyclic antidepressant overdose, this is seemingly the first description of its successful use in caffeine toxicity.