Myxedema coma (MC) is a decompensated state of hypothyroidism characterized by diminished mental status, thermal dysregulation, hemodynamic compromise, and other hypothyroid signs and symptoms that can lead to a fatal outcome if not recognized and treated promptly. It is commonly seen in older women in the winter months. It should be suspected in a clinically hypothyroid patient with altered mentation, hypothermia, hypotension, and bradycardia. There are myriad neurocognitive, cardiac, respiratory, renal, and other manifestations that serve as clinical clues in evaluating patients with suspected MC. Diagnosis is clinical and confirmed by biochemical analysis including thyroid function tests and determination of the precipitant. Clinical suspicion for MC should prompt urgent treatment with supportive cardiopulmonary measures, glucocorticoids for treatment of possible undiagnosed, concomitant adrenocortical deficiency, thyroid hormone supplementation, and management of inciting factors.