Malignant hyperthermia (MH) is a medical emergency that all perioperative nurses should be prepared to handle. Patients with the inherited MH trait have a rare skeletal muscle disease that causes them to develop life-threatening hyperthermia (ie, body temperatures of 43.3 degrees C [110.0 degrees F] or higher) at the time MH-triggering agents are administered to induce general anesthesia or shortly thereafter. The incidence of MH episodes is reported to be 1 in every 12,000 pediatric anesthetic procedures and 1 in every 40,000 adult anesthetic procedures. The MH syndrome also is characterized by continuous skeletal muscle rigidity, hypermetabolism, hypercapnia, tachypnea, and tachycardia that result in cardiac arrest and death if left untreated. Perioperative staff members' knowledge of MH, the care of MH-susceptible patients, and adequate preparation for MH crises are the cornerstones of successful patient outcomes to this life-threatening syndrome.