Pharmacologic stress myocardial perfusion imaging is being performed with increasing frequency over exercise stress. Dipyridamole and adenosine have a high side-effect profile, provide higher than needed coronary artery flow rates, and use a relatively complicated method of administration. Based on preclinical animal work, three selective adenosine A2A receptor agonists, regadenoson (CVT3146), binodenoson (MRE0470 or WRC0470), and apadenoson (BMS068645 or ATL146e), may overcome these limitations and are now in Phase III studies as pharmacologic stress agents. For single-photon emission CT imaging, binodenoson and regadenoson were concordant with adenosine images for detection and quantitation of ischemia. Despite the high A2A selectivity of binodenoson and regadenoson in preclinical studies, subjective side effects attributable to other adenosine receptor subtypes were still observed in human studies and are similar to or slightly lower than adenosine. There have been no reports of atrioventricular block or bronchospasm with either regadenoson or binodenoson in published trials.