More than a decade of dramatic changes in US and global health care has affected the practice of and payment for nuclear cardiology services. The clear diagnostic and prognostic power of nuclear cardiology procedures to detect coronary artery disease and predict patient outcomes has resulted in the rapid growth of these procedures in clinical practice. This has focused the attention of public and private payers on the high use of medical resources required to carry out nuclear cardiology testing. Two recent, major multicenter trials, one in the United States and another in Europe, have demonstrated the cost effectiveness of stress myocardial perfusion imaging strategies compared with coronary angiography in patients with known or suspected coronary artery disease, across the spectrum of pretest risks and both sexes. These studies, and more extensive data from more than 10 years of decision analysis, have reinforced the value of nuclear cardiology in modern cardiovascular health care. Future challenges will include assurance of provider and laboratory quality in the burgeoning outpatient imaging centers across the country, and wider acceptance by payers and expert panels of the evidence supporting the cost effectiveness of nuclear cardiology in most clinical settings.