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Sanchis-Gomar, F, Garcia-Gimenez, JL, Perez-Quilis, C, Gomez-Cabrera, MC, Pallardo, FV, and Lippi, G. Physical exercise as an epigenetic modulator: Eustress, the “positive stress” as an effector of gene expression. J Strength Cond Res 26(12): 3469–3472, 2012—Physical exercise positively influences epigenetic mechanisms and improves health. Several issues remain unclear concerning the links between physical exercise and epigenetics. There is growing concern about the negative influence of excessive and persistent physical exercise on health. How an individual physically adapts to the prevailing environmental conditions might influence epigenetic mechanisms and modulate gene expression. In this article, we put forward the idea that physical exercise, especially long-term repetitive strenuous exercise, positively affects health, reduces the aging process, and decreases the incidence of cancer through induced stress and epigenetic mechanisms. We propose herein that stress may stimulate genetic adaptations through epigenetics that, in turn, modulate the link between the environment, human lifestyle factors, and genes.