Over the past 15 yr, numerous clinical studies have validated the use of myocardial perfusion imaging with 201Tl for detection and evaluation of coronary artery disease (CAD). In addition, 201Tl scintigraphy plays a valuable role in the risk stratification of patients with suspected or known CAD to determine prognosis. Typical protocols involve a comparison of stress and rest images to locate regions of myocardial ischemia. Results are comparable from protocols that employ either exercise stress or pharmacologic stress. By combining 201Tl scintigraphic criteria with electrocardiographic (ECG) data, the sensitivity for detection of ischemia may be increased by as much as 25%-30%. The introduction of quantitative interpretation and SPECT has increased the accuracy of myocardial perfusion imaging with 201Tl. With respect to prognosis, several 201Tl scan variables, such as multiple perfusion defects and abnormal 201Tl lung uptake, are associated with high risk. Even when cardiac catheterization findings are known, 201Tl scintigraphy provides important supplementary information for identifying high-risk subgroups of patients with CAD.