Approximately, 10 million stress myocardial perfusion images (MPI) are performed each year in the Unites States for the diagnosis of coronary artery disease (CAD) and risk assessment. Pharmacologic stress accounts for nearly 40% of these studies, and adenosine is the most widely used stress agent at present. The relative role of adenosine versus the newer and as of yet unapproved selective A-2 agonist is currently under intense study. The purpose of this review is to critically assess the role and utility of combined exercise and adenosine, so called hybrid stress testing (HST). The discussion will focus on adenosine, because HST of other combinations is well accepted such as dobutamine plus atropine and exercise combined with dipyridamole.