The incidence and mortality of heart disease are the highest among all diseases all over the world, and are still increasing with a world wide rise in living standards. To find effective treatments for prevention and curing heart disease, it is important to understand the mechanisms behind the cause and the development of the disease. Increasing evidences have shown that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in the initiation and progression of heart disease. The potential of using antioxidants, especially the natural antioxidants, in preventing and curing the disease has attracted enormous interest. In this paper we reviewed the progress made in understanding the oxidative stress caused by myocardial ischemia-reperfusion and the cardioprotective effect of natural antioxidants against ischemia-reperfusion injury.