Temperature increases due to climate changes and operations expected to be conducted in hot environments make heat-related injuries a major medical concern for the military. The most serious of heat-related injuries is exertional heat stroke (EHS). EHS generally occurs when health individual perform physical activity in hot environments and the balance between body heat production and heat dissipation is upset resulting in excessive body heat storage. Blood flow to the skin is increased to assist in dissipating heat while gut blood flow is considerably reduced, and this increases the permeability of the gastrointestinal mucosa. Toxic materials from gut bacteria leak through the gastrointestinal mucosa into the central circulation triggering an inflammatory response, disseminated intravascular coagulation (DIC), multiorgan failure, and vascular collapse. In addition, high heat directly damages cellular proteins resulting in cellular death. In the United States military, the overall incidence of clinically diagnosed heat stroke from 1998 to 2017 was (mean ± standard deviation) 2.7 ± 0.5 cases/10,000 Soldier-years and outpatient rates rose over this period. The cornerstone of EHS diagnosis is recognition of central nervous dysfunction (ataxia, loss of balance, convulsions, irrational behavior, unusual behavior, inappropriate comments, collapse, and loss of consciousness) and a body core temperature (obtained with a rectal thermometer) usually >40.5°C (105°F). The gold standard treatment is whole body cold water immersion. In the field where water immersion is not available it may be necessary to use ice packs or very cold, wet towels placed over as much of the body as possible before transportation of the victim to higher levels of medical care. The key to prevention of EHS and other heat-related injuries is proper heat acclimation, understanding work/rest cycles, proper hydration during activity, and assuring that physical activity is matched to the Soldiers' fitness levels. Also, certain dietary supplements (DSs) may have effects on energy expenditure, gastrointestinal function, and thermoregulation that should be considered and understood. In many cases over-motivation is a major risk factor. Commanders and trainers should be alert to any change in the Soldier's behavior. Proper attention to these factors should considerably reduce the incidence of EHS.