Coronary artery disease (CAD) is the most common and important cause of ischemic heart disease, with major implications on global morbidity and mortality. Non-invasive testing is crucial in the diagnostic and prognostic work-up of patients with or at risk of CAD, and also to guide decision making in terms of pharmacologic and revascularization therapy. The traditional paradigm is to view anatomic (i.e., coronary computed tomography) and functional imaging (e.g., myocardial perfusion scintigraphy) tests as opposing alternatives. Such approach is too reductionist and does not capitalize on the strengths of each type of test while risking to overlook the inherent limitations. The combination of anatomic and functional tests in a logic of hybrid imaging holds the promise of overcoming the limitations inherent to anatomic and functional testing, enabling more accurate diagnosis, prognosis, and guidance for revascularization in patients with CAD.