Myocardial infarction (MI) is caused by deprivation of oxygen and nutrients to the cardiac tissue due to blockade of coronary artery. It is a major contributor to chronic heart disease, a leading cause of mortality in the modern world. Oxygen is required to meet the constant energy demands for heart contractility, and also plays an important role in the regulation of heart function. However, reoxygenation of the ischemic myocardium upon restoration of blood flow may lead to further injury. Controlled oxygen delivery during reperfusion has been advocated to prevent this consequence. Monitoring the myocardial oxygen concentration would play a vital role in understanding the pathological changes in the ischemic heart following myocardial infarction. During the last two decades, several new techniques have become available to monitor myocardial oxygen concentration in vivo. Electron paramagnetic resonance (EPR) oximetry would appear to be the most promising and reliable of these techniques. EPR utilizes crystalline probes which yield a single sharp line, the width of which is highly sensitive to oxygen tension. Decreased oxygen tension results in a sharpening of the EPR spectrum, while an increase results in widening. In our recent studies, we have used EPR oximetry as a valuable tool to monitor myocardial oxygenation for several applications like ischemia-reperfusion injury, stem-cell therapy and hyperbaric oxygen therapy. The results obtained from these studies have demonstrated the importance of tissue oxygen in the application of stem-cell therapy to treat ischemic heart tissues. These results have been summarized in this review article.