This chapter focuses on the more critical presentations of hyperthermia, including heatstroke and toxicological hyperthermia. Rectal temperature should be obtained on all patients with a concern for hyperthermia. A head CT followed by lumbar puncture should be performed in patients presenting with hyperthermia and neurological dysfunction in whom the diagnosis of heatstroke is not clearly established. Cooling measures should be initiated even before any investigations into the etiology of the hyperthermia. Malignant hyperthermia (MH) is a disease state occasionally observed in patients undergoing general anesthesia. The hypercatabolic state results in rapid-onset, severe hyperthermia (greater than 40.5 degree Celsius), tachycardia, and tachypnea. Another pathological condition in which hyperthermia is encountered is neuroleptic malignant syndrome (NMS). It is caused by excessive blockage of dopaminergic receptors by some antipsychotics, as well as by the withdrawal of dopaminergic drugs. Neuromuscular blockade can be used for refractory hyperthermia or for airway management.