Aging is a complex process associated with progressive damage that leads to cellular dysfunction often accompanied by frailty and age-related diseases. Coping with all types of physiologic stress declines with age. While representing a primordial, cross-species response in poikilo- and homeotherms, the age-dependent perturbation of the stress response is more complex than previously thought. This short review examines how age influences the stress axis at multiple levels that involve both activating and attenuating pathways.