Calcium channel antagonists (CCAs) are commonly involved in drug overdoses. Standard approaches to the management of CCA overdoses, including fluid resuscitation, gut decontamination, administration of calcium, glucagon, and atropine, as well as supportive care, are often ineffective. We report on two patients who improved after addition of hyperinsulinemia-euglycemia (HIE) therapy. We conclude with a literature review on hyperinsulinemia-euglycemia therapy with an exploration of the physiology behind its potential use.