Both multicrystal and single-crystal detectors have been in use for more than 25 years for measurement of ejection fraction by analysis of images collected during the first-pass transit of radionuclides through the heart. Originally, multicrystal cameras were preferred, because they provided higher count rates than Anger cameras; however, over the years improvements in count rate capability and collimator design have enabled Anger cameras to perform equally well. This has become an important issue now that readily available 99mTc agents, such as sestamibi, enable evaluation of both myocardial function and perfusion from a single injection. The technical abilities of a particular camera determine which acquisition protocols are most likely to provide clinically useable images for the widest spectrum of patients. Electrocardiographic-gated list mode collection is highly desirable for first-pass imaging, providing the greatest flexibility of data review, rebinning, and analysis. Attention to quality control issues of data characterization and processing is important to ensure accuracy and precision of all measurements. Accurate determinations of ejection fraction of the left ventricle are possible routinely and, under favorable circumstances, of the right ventricle as well.