Cardiac muscle is frequently affected by many stimuli responsible for loss of cell homeostasis, including physical exercise. While exercise has been presented as a recommended activity for health reasons, it also provides favorable conditions for additional production of reactive oxygen species. These compounds are associated with fundamental mechanisms of cell metabolism but are also related to the etiology and pathophysiology of some cardiac diseases. Cardiac muscle tissue has a high oxidative metabolic rate and relatively low activity of the main antioxidant enzymes, which could enhance its susceptibility to oxidative injury after acute exercise. However, physical training could be considered an important stimulus for the different antioxidant systems like glutathione and those related to the activity of some important antioxidant enzymes in myocardial protection such as superoxide dismutase and glutathione peroxidase. Endurance training seems to induce up-regulation in some antioxidant defenses, protecting cardiac muscle in potentially harmful situations that induce additional oxidative stress. Nevertheless, the mechanisms related to this cross-tolerance effect of training are not yet well understood.