Patients presenting with chest pain and related symptoms account for over 6 million emergency department (ED) visits in the United States annually. However, less than 5% of these patients are ultimately diagnosed with acute coronary syndrome (ACS). ED clinicians face the diagnostic challenge of promptly identifying and treating these high-risk patients amidst the overwhelming majority of lower-risk patients for whom further testing and/or treatment is either unnecessary or non-urgent. To assist with and expedite risk stratification and decision-making in this challenging clinical scenario, diagnostic tools like clinical risk scores and high-sensitivity serum biomarkers have been incorporated into care algorithms within the ED. In this narrative review, we discuss how these tools impact the appropriate use of cardiovascular imaging in the initial assessment of patients presenting to the ED with possible ACS.