Thallium-201 was the original and the only myocardial perfusion imaging (MPI) tracer, first for planar (1973) and later for SPECT imaging (1980s), for almost 15 years. Introduction of Tc-99m-based tracers (sestamibi-1984, tetrofosmin-1989) knocked Tl-201 from the pedestal. The advantages of Tc-99m-based agents became obvious: higher energy (140 keV vs 69-80 keV), shorter half-life (6 hours vs 72 hours), flexibility of imaging protocols (due to lack of meaningful Tc-99m redistribution), and local production of the tracer (using molybdenum generator vs dose delivery of . The higher energy Tc-99m gamma rays and a shorter half-life increased the acquired count density, and thus improved the quality of both perfusion and gated images compared to Tl-201.The advent of coronary CT angiography (CTA) and the exponential increase of MPI volume unleashed the previously non-existent debate pointing to possible longterm harmful effects of low-dose radiation used for diagnostic imaging. 1 CTA technology evolved and answered rapidly with a substantial decrease in radiation exposure. 2 Migration from Tl-201 to Tc-99m by the nuclear cardiology community was driven more by the ease of use of Tc-99m-based tracers, rather than by fear of substantially higher per study radiation exposure of Tl-201 (15 mSv vs 9-11 mSv). Most recently, the majority of criticism was aimed at dual-isotope protocols (Tl-201 rest/Tc-99m stress), which result in the highest radiation exposure per study (22-23 mSV) not offset by a relatively modest decrease of the length of the test. 3 Using standard imaging technology (Anger camera) and standard Tl-201 doses (3-4 mCi), some advantageous Tl-201 characteristics remain:(1) Tl-201 is by design ''stress-first imaging.'' 4 Immediate review of stress images may reveal normal perfusion or an unexpectedly abnormal result such that the rest/redistribution portion of the test may then be avoided. This would significantly decrease the length of the test (from 4-6 hours to 1 hour) and additionally decrease radiation exposure to the laboratory personnel and to accompanying visitors. 5 (2) As Tl-201 is excreted by the kidneys, high subdiaphragmatic tracer accumulation is not an issue, compared to the gastrointestinal excretion of Tc-99m. (3) Flow to uptake linearity is better preserved with Tl-201 compared to Tc-99m-labeled tracers. This is of particular importance with the use of coronary vasodilators. Coronary blood flow increases by non-physiologic amounts (200-300%) with vasodilators, compared to approximately 100% with moderate exercise. (4) Tl-201 remains a preferred ''viability tracer'' due to its ability to visualize severely dysfunctional myocytes. Tl-201 crosses the cellular membrane, while Tc-99m tracers are transported into the mitochondria, an organelle more susceptible to ischemic damage. (5) Because of early post-stress imaging, Tl-201 lung uptake can be quantified and used as a surrogate for pulmonary capillary wedge pressure. (6) Past and likely future Tc-99m shortages will lead either to the abandonmen...