Nuclear cardiology is the time-honored offspring of the marriage between nuclear technology and coronary physiology [1]. Several imaging paradigms later endorsed by stress echocardiography were first understood, proposed, and popularized by nuclear cardiology: the merit of imaging cardiac function during stress, in lieu of the simple electrocardiogram; the value of the pharmacological alternative to physical exercise for stressing the heart; the need to assess viability in segments with resting dysfunction; the advantage of routine use of digital handling for data acquisition, storage, and display; and the prognostic impact of extent and severity of stress-induced ischemia [2]. Although the comparison of nuclear cardiology and echocardiography previously involved a fundamental philosophical issue between the diagnosis of coronary disease based on perfusion (hence the possibility of influencing these data on the basis of small vessel disease, hypertrophy, and other causes of abnormal coronary flow reserve) and evidence of ischemia (hence less sensitivity to mild disease that may engender submaximal attainment of flow without ischemia), recent advances have made it possible for both techniques to offer function and coronary flow reserve data [3]. Each technique has adopted various technical advances, which include a “methodological drift”to incorporate information previously used by the other; thus, gated single-photon emission computed tomography (SPECT), ventriculography, and attenuation correction have been added to SPECT [4], while harmonic imaging, pulsed Doppler coronary flow reserve, diastolic and valvular evaluation, myocardial contrast, and real-time three-dimensional (3D) imaging have been added to echocardiography [5]. These technical advances have provided particular benefits to subpopulations, although it seems unlikely that the few percentage point changes to overall sensitivity and specificity will render obsolete the general conclusions derived from comparison of the methods over the last 30 years, upon which this chapter is based.