Stress echocardiography integrates comprehensive echocardiography with physical, pharmacological, or electrical stress to evaluate the different vulnerabilities of the patient, from epicardial artery stenosis to diastolic reserve, from cardiac systolic reserve to coronary microcirculation and cardiac autonomic function. Formerly, the assessment of regional wall motion abnormality was the singularly widespread practice during stress echo as the specific diagnostic marker of an ischemia-producing epicardial coronary artery stenosis. In the contemporary ABCDE protocol, regional wall motion abnormality persists as the primary focus in step A. Subsequent steps include the evaluation of diastolic function and pulmonary B-lines in step B; assessment of left ventricular contractile and preload reserve through volumetric echocardiography in step C; determination of Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and evaluation of ECG-based heart rate reserve and ST segment changes in the non-imaging step E. These five biomarkers converge, both conceptually and methodologically, within the ABCDE protocol, enabling a thorough risk stratification of patients with chronic coronary syndromes and/or heart failure. The widespread availability of echocardiographic equipment across medical centers has been pivotal for the dissemination of this technique, particularly considering its cost-effectiveness, absence of radiation, and minimal environmental impact.