Heat-related illnesses encompass a spectrum of disorders resulting from exposure to high temperatures and the body's inability to efficiently dissipate heat. These syndromes range from mild illnesses, such as heat edema, heat rash, and heat cramps, to more concerning manifestations such as exercise-associated collapse, heat exhaustion, and exertional rhabdomyolysis. The most severe and potentially life-threatening heat-related illnesses include exercise collapse associated with sickle cell trait, severe exercise-associated hyponatremia, and heat stroke. Common risk factors of heat-related illness are physical activity in high ambient temperatures, behavioral factors, lack of acclimatization, deconditioning, recent illness, inadequate hydration, predisposing medical conditions, use of certain drugs and supplements, and excessive clothing or equipment. Treatment of mild heat-related illness includes cessation of activity, removal of the patient from high temperatures, and oral hydration. Symptoms of heat exhaustion are nonspecific and may include the inability to continue physical activity, weakness, fatigue, headache, nausea, and vomiting. Management includes rest, hydration, and basic cooling measures. Heat stroke is a medical emergency requiring immersion in ice-cold water within 30 minutes to prevent significant morbidity and mortality. Diagnosis of severe exercise-associated hyponatremia and exercise collapse associated with sickle cell trait require a high index of suspicion because they can mimic heat stroke but require different treatments. Heat-related illnesses are largely preventable with proper acclimatization, adequate hydration, avoidance of physical activity in extreme temperatures, and promotion of population-based intervention programs, particularly during anticipated heat waves.