The past few years have witnessed impressive advances in the field of noninvasive cardiac imaging. For example, computed tomography (CT) coronary angiography has been adopted into daily clinical routine and, at least in some patient populations, is challenging the role of invasive angiography as the anatomic standard of reference. This is because the latter is associated with a nonnegligible periprocedural morbidity and mortality, which suggests confining its use to patients who will benefit from a revascularization procedure. Many factors that are beyond the quantification of anatomic narrowing and therefore cannot be fully appreciated with morphologic assessment will eventually determine whether or not a given lesion produces stress-induced ischemia. Myocardial perfusion imaging with single-photon emission computed tomography (SPECT) is among the most widely used and well-established noninvasive tools for the diagnosis of ischemic coronary disease. It allows assessment of the physiological relevance of coronary lesions and offers a high prognostic predictive value. Although positron emission tomography (PET) may achieve a higher accuracy than SPECT, its use has so far often been limited to large centers. Recent advances in image processing software and the advent of hybrid scanners have paved the way for fusion of image datasets from different modalities. An ideal, noninvasive technique for the diagnosis of coronary artery disease should provide complementary information on coronary anatomy as well as on pathophysiologic lesion severity. SPECT/CT and PET/CT hybrid imaging can provide such unique information, which not only improves diagnostic assessment and risk stratification but may also guide decision making with regard to revascularization in patients with coronary artery disease.