The differential diagnosis of the hyperpyrexic patient in the emergency department is extensive. It includes sepsis, heat illness including heat stroke, neuroleptic malignant syndrome, malignant hyperthermia, serotonin syndrome and thyroid storm. Each of these possible diagnoses has distinguishing features that may help to differentiate one from another. However, establishing the correct diagnosis is a challenge in the setting of the obtunded emergency patient who gives no history and where there may be limited access to any past medical or drug history. This paper presents such a case and reviews the features of the differential diagnoses and management of the hyperpyrexic patient.