Iatrogenic hypoglycemia is an acute complication of insulin or sulfonylurea/glinide treated diabetes which, even when mild, (defined as a glucose value <3.9 mmol/L, or 70 mg/dL), will interfere with normal activities and can be frightening to many patients. Severe hypoglycemia is defined as that which causes cognitive impairment and requires assistance by another person to recover, and may be associated with a risk of injury to the patient or others, seizures, brain damage, and even death. This chapter covers the epidemiology, hypoglycemia and intensive blood glucose control, consequences of hypoglycemia in the treatment of diabetes, risk factors for hypoglycemia, and hypoglycemia mitigation strategies. More intensive blood glucose control is associated with a reduction in microvascular complications, and, after sufficient follow-up, cardiovascular complications, of patients with either T1DM or T2DM. Studies have generally defined intensive blood glucose control as a HbA1c of at approximately 7%, compared to control groups having HbA1c values of 8–9%, at trial’s end.