Traditionally, ST segment depression has been associated with acute coronary syndromes; this electrocardiographic pattern may also be found in patients with nonischemic events, such as left bundle branch block (LBBB), left ventricular hypertrophy (LVH), and those with therapeutic digitalis levels. Using the ECG as an adjunct in distinguishing those patients with acute coronary syndromes from those with more “benign,” nonacute causes of STSD will obviously lead to divergent treatment and management plans. The following cases illustrate the use the ECG in patients presenting with chest pain and electrocardiographic ST segment depression attributable to an ACS, LVH, LBBB, or digitalis.