Sex is a potent modifier of the cardiovascular system because males and females differ in several aspects of the heart's biology and physiology. Epidemiologically, premenopausal women possess a distinct advantage over men in the occurrence of cardiovascular heart disease; however, this advantage shifts to men once a negative cardiac event has occurred. The reasons for these differences are not completely understood and are likely attributable to many factors. Nonetheless, the sex hormones seem to be important regulators of myocardial health. Of particular note, the sex hormones influence the molecular and physiological responses of the heart to the stress of exercise including the expression of several vital proteins such as the cardioprotective 70-kDa heat-shock protein, Hsp70. This review will focus on the exercise-induced expression of Hsp70 and how it is modified by sex. A better understanding of how sex, the sex hormones in particular, modifies the exercise stress response has important implications in the prescription of exercise to males and females, young or old.