Extensive experimental and comparative studies provide a solid understanding of the physiological basis of the stress response system and its variation across and within species.

However, lagging behind this is a formal theoretical framework to help unify the wealth of existing verbal hypotheses linking stress response mechanisms and fitness, and to explain how such a response system has evolved.

We propose an evo-mecho approach, combining optimality models and evolutionary simulations with empirical evidence about the underlying physiology, to show how mechanistic constraints and the predictability of environmental risks shape the stress response.

A deeper understanding of stress response evolution will require mechanistically informed evolutionary models, phylogenetically controlled comparative analyses, and experimental evolution studies.