Heatstroke is a common veterinary emergency that, depending on the severity of injury, can progress to a life-threatening condition. Heatstroke can be classic (nonexertional) or exertional. Classic heatstroke develops when the body is exposed to high external temperatures, whereas exertional heatstroke is caused by strenuous exercise. Thermoregulation is the intrinsic ability of the body to maintain core body temperature within normal limits through an intricate balance of heat conservation and heat dissipation. Severe disease ensues when persistent hyperthermia causes injury to the body for which these mechanisms can no longer adequately compensate. The first stages of heatstroke are characterized by initial thermoregulation, acute phase response, and activation of heat shock proteins. The organ systems most commonly affected during heatstroke are the gastrointestinal tract and the coagulation, renal, cardiac, pulmonary, and central nervous systems.