Malignant hyperthermia (MH) is a rare but potentially fatal disorder characterized by a hypermetabolic state produced by exposure to triggering agents such as volatile anesthetics and succinylcholine.^1,2 MH crises have also been recognized in the absence of exposure to obvious triggers. The incidence of MH may range from 1:5,000 to 1:100,000 anesthetic administrations, although the prevalence of predisposing genetic lesions is likely as common as 1 in every 3,000 individuals.¹ Clinically, MH presents with a constellation of signs and symptoms, including muscle rigidity, hypercarbia, tachycardia, acidosis, and hyperthermia, which, if not promptly recognized and managed with dantrolene, is likely to lead to significant morbidity or death.^1,2 Further complicating the diagnosis and treatment of MH is the potential for symptoms to develop while on cardiopulmonary bypass during cardiac surgery, when the patient’s vital signs and temperature are being dramatically manipulated and when metabolic disturbances that would otherwise be abnormal are anticipated. In this article, we review a case of suspected MH during cardiac surgery, discuss the challenges associated with treatment and diagnosis, and review the differential diagnosis of the patient’s presentation.