The recently reported ISCHEMIA trial will reignite the debate regarding the optimal first diagnostic test when evaluating chest pain in patients suspected to have coronary artery disease. This article considers whether the debate should be refocused even before selecting any diagnostic test. The case is made to prioritize risk factor management and empiric angina pectoris control as part of optimal secondary prevention followed by expeditious clinical reassessment to determine adequacy of therapeutic responses, including quality of life, before embarking on diagnostic testing. Once anatomical coronary artery disease is known in diagnostic algorithms that incorporate cardiac computed tomographic angiography, there is the potential to forego an adequate trial of conservative management, thereby failing to translate the key finding of ISCHEMIA to practice. Embedded in this “Symptom-driven Path” is the principle that definitive diagnostic testing must be expeditious if symptoms persist or deteriorate and impair quality of life during conservative management. This strategy would ensure appropriate utilization of contemporary conservative management which is replete with numerous effective pharmacotherapies that modify atherosclerosis and dramatically reduce cardiovascular risk. In conclusion, diagnostic testing and invasive therapy would be minimized and dictated primarily by adequacy of patient symptoms and quality of life.Copyright © 2020 Elsevier Inc. All rights reserved.