Cardiopulmonary exercise testing (CPET) is a well-accepted physiologic evaluation technique in patients diagnosed with heart failure and in patients presenting with unexplained dyspnea on exertion. Several variables obtained during CPET, including oxygen consumption relative to heart rate and work rate provide consistent, quantitative patterns of abnormal physiologic responses to graded exercise when left ventricular dysfunction is caused by myocardial ischemia. This concept report describes both the methodology and clinical application of CPET associated with myocardial ischemia. Initial evidence indicates left ventricular dysfunction induced by myocardial ischemia may be accurately detected by an abnormal CPET response. CPET testing may complement current noninvasive testing modalities that elicit inducible ischemia. It provides a physiologic quantification of the work rate, heart rate, and O(2) uptake at which myocardial ischemia develops. In conclusion, adding CPET with gas exchange measurements is likely to be of value in diagnosing and quantifying both overt and occult myocardial ischemia and its reversibility with treatment.