Background: During the 2003 French heatwave 15 000 excess deaths were registered. One fifths died from the combination of dehydration, heatstroke, and hyperthermia and one tenth from dehydration, despite abundant water. Methods and Results: We hypothesized that physiologic adaptation to heat was not effective in the victims attributable to side-effects of drugs (impaired thermoregulation, suppressed thirst) many of these patients were taking. This could explain why many victims died of dehydration despite availability of water. As a consequence of the global climate change heatwaves may occur more frequently and may be more intense, with a strong impact on the future selection of drugs in elderly patients. Conclusion: Insufficient water intake, impaired thermoregulation, and resulting death may be directly linked to the use of certain drugs, implying an immediate need for public awareness during heatwaves and for long-term strategies to mitigate the expected increase in future heatwave-related fatalities.