We report a case of a 53-year-old man whose first manifestation of coronary artery disease was an acute isolated posterior myocardial infarction (IPMI). Acute IPMI is relatively uncommon and predominantly due to occlusion of the left circumflex coronary artery. IPMI is challenging to diagnose due to the absence of ST segment elevation on a standard 12-lead electrocardiogram (ECG) even in the setting of total coronary artery occlusion and transmural (Q-wave) infarct. We discuss the diagnostic implications of the absence of tall R waves in leads V1 and V2 on this patient’s ECG. The utility of posterior leads (V7 through V9) is demonstrated. The controversy surrounding the use of thrombolytic therapy or primary angioplasty in the setting of acute IPMI without ST segment elevation on a standard 12-lead ECG is reviewed.