Although thallium exercise imaging has served an important role in clinical cardiology, it is significantly limited by suboptimal sensitivity and specificity, particularly in asymptomatic man. The increasing recognition of silent myocardial ischemia, the significant prevalence of coronary artery disease in asymptomatic middle age men, and the frequent occurrence of myocardial infarction without preceding symptoms in 60% of cases emphasizes the need for a more definitive, noninvasive diagnostic test for the presence of coronary artery disease suitable for screening in asymptomatic or symptomatic patients. Intravenous dipyridamole combined with handgrip stress provides a potent stimulus for purposes of diagnostic perfusion imaging. Although planar and single photon emission computed tomography (SPECT) imaging also have played an important role, these techniques are seriously hindered by their inability to quantitate radiotracer uptake or image modest differences in maximum relative flow caused by coronary artery stenosis. Accordingly, the combination of dipyridamole-handgrip stress with positron imaging of myocardial perfusion has become a powerful diagnostic tool suitable for routine clinical use. With the availability of generator-produced rubidium-82, dedicated clinically oriented positron cameras, the routine application of positron imaging to clinical cardiology has become feasible. Based on published literature, the current clinical indications for positron imaging that may be carried out economically on a routine clinical basis include assessment of myocardial perfusion utilizing rubidium-82 or N-13 ammonia for purposes of reliable, accurate, noninvasive screening for coronary artery disease in symptomatic or asymptomatic patients; assessing noninvasively the physiologic severity of coronary stenoses; myocardial infarct imaging; assessing myocardial viability of reversibly injured or ischemic cells using N-13 ammonia combined with fluorine-18-deoxy-glucose or Rubidium-82 alone in experimental animals; assessing regional or global left ventricle (LV) function by 3-dimensional gated blood pool imaging and/or wall thickening by ECG gating; and assessing the functional significance of collaterals in man.