This article reviews causes of marathon collapse related to physical exhaustion, heat exhaustion and dehydration. During severe exercise-heat stress (high skin and core temperatures), cardiac output can decrease below levels observed during exercise in temperate conditions. This reduced cardiac output and vasodilated skin and muscle can make it difficult to sustain blood pressure and perhaps cerebral blood flow. Dehydration can accentuate this cardiovascular strain. In contrast, excessive heat loss to the environment during cold weather may result in hypothermic collapse. Other factors contributing to post-race collapse might include reduced skeletal muscle pump activity and dehydration and prior heat stress mediated changes in cerebrovascular responses to orthostatic challenges.