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Purpose: The objectives of this review were to: (1) identify the acute cardiovascular responses to aerobic exercise used in an exercise stress test (EST), (2) identify when and how to best conduct an EST including the stopping point, (3) identify conditions that would preclude an EST, (4) define the limiting signs and symptoms associated with an EST (5), discuss what data are needed as part of an EST and how to interpret EST data. Methods: We identify the cardiovascular responses to an EST and when an EST should or should not be used. Finally we analyze the components of an EST and potential sensitivities, significances and predictability of the changes in the outcome data that will provide diagnosis overt cardiovascular disease, and for purposes of exercise prescription and evaluation of rehabilitation effects in cardiac patients. Results: Although most of the focus for performing an EST traditionally has been on the diagnostic value to identify ST-segment abnormalities, an EST provides other valuable diagnostic and prognostic data including maximal oxygen consumption (predicted or measured), exercise capacity and fatigability, blood pressure and heart rate responses to exercise and recovery. Conclusions: This review identifies the most recent standards, and guidelines of EST, which include the acute physiological response of the cardiovascular system to aerobic exercise, the use of EST in evaluation of coronary artery disease, an updated diagnostic and prognostic variables of EST, and reporting of EST. Condensed abstract: This review identifies the most recent standards, and guidelines of the exercise stress test (EST), which include the acute physiological response of the cardiovascular system to aerobic exercise, the use of EST in evaluation of coronary artery disease, diagnostic and prognostic variables of EST, and reporting of EST. Introduction An exercise stress test (EST) is commonly used for the diagnosis and evaluation of cardiac disease. In addition, EST is often used to evaluate the effects of pharmacological medication on whole body function, and for exercise prescription in diseases and conditions that include but are limited to cardiac rehabilitation, obesity, diabetes and various neuropathies. EST is typically conducted using a treadmill or a cycle ergometer, while monitoring the electrocardiogram (ECG) [1], ventilatory threshold [2], blood pressure (BP) [3], heart rate (HR) [4], oxygen consumption [5], general patient self-reported effort (e.g., by a Borg Scale test) and physical appearance—including chest pain and dyspnea [6]. The American College of Cardiology (ACC), American Heart Association (AHA), American College of Sports Medicine (ACSM) and the American Society of Nuclear Cardiology all recommend an EST for diagnosing patients who are at risk for obtaining cardiovascular disease (CAD). An EST can be conducted on the majority of patients who can exercise, irrespective of age or sex [7], but some of the guidelines for athletes may need some modifications [8]. This review provides an overview of the most recent standards, and guidelines of EST, which include the acute physiological response of the cardiovascular system to aerobic exercise, the use of EST in evaluation of CAD, updated diagnostic and prognostic variables of EST, and modern reporting of EST. These guidelines are intended for healthcare professionals who currently use or are considering incorporating EST as part of health care evaluation, and rehabilitative delivery to their patients. Review of relevant literature Acute cardiovascular response to aerobic exercise used in an exercise stress test EST incorporates acute aerobic exercise, which induces a requirement for increasing oxygen delivery to meet the challenges of increasing work, and to match this with sufficient perfusion of blood to the working musculature to remove the metabolic byproducts that are generated as a result of substrate utilization to generate ATP [9]. The amount of oxygen delivered to and consumed by the working skeletal muscle increases with the intensity of the exercise. Furthermore, Correspondence to: Salaheddin Sharif MS, Department of Physiology, Faculty of Medicine, University of Benghazi, Benghazi Libya; Tel: 00218 945768092; E-mail: salaheddin.sharif@uob.edu.ly Received: June 20, 2016; Accepted: June 26, 2016; Published: July 31, 2016 Sharif S (2016) The diagnostic value of exercise stress testing for cardiovascular disease is more than just st segment changes: A review J Integr Cardiol, 2016, doi: 10.15761/JIC.1000173 Volume 2(4): 341-355 ventilation of expired gases increases with elevated workloads to both dispose of the greater levels of carbon dioxide, produced by increased metabolism, and to buffer lactic acid/hydrogen ions produced during the EST. Many cardiorespiratory and hemodynamic mechanisms function collectively to support increased aerobic requirement of exercise. To maximize oxygen delivery, blood flow to the working muscles increases while non-essential tissues experience a concomitant sympathetic vasoconstriction resulting in a reduction of blood flow [10]. This maximizes the distribution of cardiac output the exercising muscles [11]. The overall effect of changes include modifications of heart rate, stroke volume, cardiac output, blood flow, blood pressure and arteriovenous oxygen difference [12-14].