Poor R-wave progression is a common ECG finding that is often inconclusively interpreted as suggestive, but not diagnostic, of anterior myocardial infarction (AMI). Recent studies have shown that poor R-wave progression has the following four distinct major causes: AMI, left ventricular hypertrophy, right ventricular hypertrophy, and a variant of normal with diminished anterior forces. Standard ECG criteria that identify and distinguish these causes have been developed. An interpretive approach to the ECG with poor R-wave progression is presented that has clinical relevance in the daily treatment of patients.