Respiratory failure in myxedema is a complex medical emergency and may require prolonged ventilatory assistance. Appropriate management of this medical problem requires an understanding of its effects on the central nervous system and peripheral neuromusculoskeletal system. Weaning of these patients can be very protracted and requires a diligent multidisciplinary approach. Because of its infrequency, ventilatory management of severe hypothyroidism has not been studied in a controlled fashion. The first part of this review discusses the mechanisms of respiratory failure in myxedema. The second part explores strategies in mechanical ventilation and weaning of myxedematous patients.