The marathon poses a considerable physical challenge for athletes of all levels. When combined with high heat and humidity, not only is performance potentially compromised, but health and well-being are also at risk. There are well recognised effects of heat and hydration status on the cardiovascular and thermoregulatory systems that can account for the decreased performance and increased sensation of effort that are experienced when competing in the heat. Elevated exercise heart rate and core temperature at the same absolute exercise intensity are commonly reported. Dehydration occurring during exercise in the heat and results in reductions in stroke volume, cardiac output and blood pressure, as well as a marked decline in blood flow to the working muscles. Recent work suggests that hyperthermia may have a direct affect on the CNS and the brain may contribute to fatigue during prolonged exercise in a warm environment. At present, evidence supports a significant role of catecholaminergic neurotransmission, but there are a number of metabolic and circulatory perturbations occurring within the brain that may also be important in the fatigue process.