Severe hypoglycemia in patients with diabetes is associated with increased risk of adverse cardiovascular events and death. Recent large randomized clinical trials in individuals with type 2 diabetes have shown that intensive glycemic control may result in increased mortality, and hypoglycemia has been investigated as a possible cause. Acute hypoglycemia is a proarrhythmic, proinflammatory, and prothrombotic state, and several mechanisms have been proposed to explain how hypoglycemia might increase cardiovascular morbidity and mortality. However, data from large clinical trials do not provide strong evidence to establish hypoglycemia as a cause of increased mortality. Severe hypoglycemia is also a marker of frailty and a predictor of adverse outcomes in patients with diabetes. Individualized therapy should be the goal in patients with diabetes to avoid severe hypoglycemia and any related adverse outcomes.