A rise in body core temperature and loss of body water via sweating are natural consequences of 35 prolonged exercise in the heat. This review provides a comprehensive and integrative overview of how 36 the human body responds to exercise under heat stress and the countermeasures that can be adopted to 37 enhance aerobic performance under such environmental conditions. The fundamental concepts and 38 physiological processes associated with thermoregulation and fluid balance are initially described, 39 followed by a summary of methods to determine thermal strain and hydration status. An outline is 40 provided on how exercise-heat stress disrupts these homeostatic processes, leading to hyperthermia, 41 hypohydration, sodium disturbances and in some cases exertional heat illness. The impact of heat stress 42 on human performance is also examined, including the underlying physiological mechanisms that 43 mediate the impairment of exercise performance. Similarly, the influence of hydration status on 44 performance in the heat and how systemic and peripheral hemodynamic adjustments contribute to fatigue 45 development is elucidated. This review also discusses strategies to mitigate the effects of hyperthermia 46 and hypohydration on exercise performance in the heat, by examining the benefits of heat acclimation, 47 cooling strategies and hyperhydration. Finally, contemporary controversies are summarized and future 48 research directions provided.