Extensive work has already been performed with regard to both planar and single photon emission computed (SPECT) technetium 99m sestamibi studies. Before widespread application of optimized acquisition and processing methods, clinical results between 99mTc sestamibi and thallium 201 were remarkably similar. It is anticipated that as techniques for 99mTc sestamibi planar and SPECT imaging become optimized, improvements in sensitivity and specificity for detection of coronary artery disease, over those observed with 201Tl, might be forthcoming. This expectation is based on the improved image quality inherent in the use of the 99mTc agent with its higher count rate and higher energy. This improvement in image quality may be a principal reason for laboratories to switch from 201Tl to 99mTc sestamibi imaging. It is anticipated that, with improved imaging characteristics, it will be easier for the average community hospital to obtain higher quality planar or SPECT imaging using 99mTc sestamibi rather than 201Tl. In addition to improved image quality, the characteristics of 99mTc sestamibi allow gated planar or SPECT perfusion images to be obtained. It has been suggested that stress-gated SPECT sestamibi studies may provide all the information contained in a stress-rest nongated 99mTc sestamibi study, thereby potentially increasing patient throughput, a major concern with SPECT. Throughput can also be increased by using dual-isotope approaches with rest 201Tl and stress technetium sestamibi acquisitions, employing either separate or simultaneous imaging with which the entire study can be accomplished in less than 2 hours. With simultaneous dual-isotope acquisition, camera time can be reduced by 50%. Finally, 99mTc sestamibi offers the advantage of the ability to perform first-pass exercise ventricular function and SPECT myocardial perfusion studies with a single injection of tracer. Regarding the assessment of myocardial viability, results to date suggest a very high degree of concordance between 201Tl and 99mTc sestamibi studies using either planar or SPECT acquisition techniques. Correlative rest studies with both tracers will be of particular interest, as will preoperative and postoperative and position emission tomography correlation studies.