Up-sloping ST-segment depression with positive T waves is increasingly recognized as a sign of regional subendocardial ischemia associated with severe obstruction of the left anterior descending coronary artery. However, it should be emphasized that a large number of patients may have ST-elevation without having acute ST-elevation acute coronary syndrome, while acute ongoing transmural ischemia due to an abrupt occlusion of an epicardial coronary artery may occur in patients with ST-elevation less than the thresholds defined by the guidelines. Patients with ST-segment elevation on their electrocardiogram and symptoms compatible with acute myocardial ischemia/infarction should be referred for emergent reperfusion therapy. ECG interpretation is an essential part of the initial evaluation of patients with symptoms suspected to be related to myocardial ischemia, along with focused history and physical examination. In other instances, changes are subtle and might be recognized only when ECG recording is repeated after changes in the severity of symptoms. At times, the changes are typical and clear. In acute coronary syndromes, the electrocardiogram (ECG) provides important information about the presence, extent, and severity of myocardial ischemia. Further studies are needed to assess the ability of various ECG criteria to accurately differentiate between STEMI and NISTE. It seems that, in the "real world," the ability of physicians to differentiate NISTE from STEMI based on the presenting ECG pattern widely varies and depends on the prevalence of baseline NISTE in the patient population. It should be remembered that patients presenting with chest pain and showing benign pattern of NISTE (eg, "early repolarization" or STE secondary to left ventricular hypertrophy) may have true ischemic pain and non-STE myocardial infarction or even STEMI on top of the baseline benign pattern. Other times, differentiating between true STEMI and NISTE may be difficult. In some cases a pattern of benign nonischemic STE (NISTE) can be recognized fairly easily. However, not all ECGs with STE necessarily reflect transmural infarction from acute thrombotic occlusion of an epicardial coronary artery, as a large number of patients presenting with compatible symptoms have baseline STE. Currently, time to reperfusion is considered to be a quality of care measure, and the latest American College of Cardiology/American Heart Association guidelines for the treatment of STE acute myocardial infarction (STEMI) emphasize that the physician at the emergency department should make reperfusion decisions within 10 minutes of performing the initial electrocardiogram (ECG). Earlier studies suggested lack of beneficial effects in patients presenting without STE and even with ST depression. It is well accepted that early reperfusion is beneficial in patients with acute myocardial infarction presenting with ST elevation (STE).