Myocardial ischemia is caused by a mismatch between myocardial oxygen supply and myocardial oxygen requirements. Obstructive coronary artery disease (CAD) is the most common cause for myocardial ischemia. Although coronary bypass graft (CABG) surgery und percutaneous coronary interventions (PCI) are established therapies to treat CAD, 10 years after CABG or PCI 40% of the patients still have angina pectoris. Besides obstructive CAD, chronic myocardial ischemia can be induced by small vessel disease and endothelial dysfunction that is not treatable with CABG or PCI. On the cellular basis myocardial ischemia leads to a sodium overload that is caused by an increase in the late sodium current (I Na, late). The increased intracellular sodium concentration leads to a mode switch of the sodium/calcium exchanger (NCX) that now eliminates sodium from the cell and transports calcium into the cell. The resulting calcium overload activates the contractile myofilaments causing an increased wall tension in diastole which compromises the microcirculation and intensifies myocardial ischemia.