The ISCHEMIA trial investigated two major principles in the therapy of coronary artery disease (CAD), i.e., symptom relief and improvement of prognosis. Specifically, it was designed to answer the question of whether, after ruling out left main stenosis, a routine interventional strategy in addition to optimal medical therapy can improve clinical outcome. Overall, this hypothesis could not be confirmed. Nevertheless, the trial yields interesting new aspects in the field of cardiac imaging. As a noninvasive diagnostic approach for individuals with suspected coronary artery disease, two different concepts are available: stress testing for ischemia (single-photon emission computed tomography, positron emission tomography, cardiac magnetic resonance imaging, stress echocardiography) and anatomic visualization of coronary artery stenosis by coronary computed tomography (CT) angiography (coronary CTA). While there was no randomized comparison between these two approaches in ISCHEMIA, the good outcome achieved by using coronary CTA as a “gatekeeper” to randomization supports the potential of coronary CTA as a diagnostic tool—both as first- and as second-line—when CAD is suspected. However, the trial also raises new questions in the field of cardiac imaging that need to be addressed in future studies.