The triage of patients presenting to the emergency department (ED) with acute chest pain is a diagnostic challenge. Radionuclide myocardial perfusion imaging has been shown to have favorable diagnostic and prognostic value in this setting, with an excellent early sensitivity to detect acute myocardial infarction (MI) not achieved by other testing modalities. A normal resting perfusion imaging study has been shown to have a negative predictive value of over 99% to exclude MI. Observational and randomized trials of both rest and stress imaging in the ED evaluation of patients with chest pain have demonstrated reductions in unnecessary hospitalizations and cost savings compared with routine care. Perfusion imaging has also been used in risk stratification after MI, and for measurement of infarct size to evaluate reperfusion therapies. Novel "hot spot" imaging radiopharmaceuticals that visualize infarction or ischemia are currently undergoing evaluation and hold promise for future imaging of acute coronary syndromes.