Abstract Patients with acute coronary syndromes (ACS), particularly non-ST-segment elevation ACS, represent a spectrum of patients at variable risk of short- and long-term adverse clinical outcomes. Accurate prognostic assessment in this population requires the simultaneous consideration of multiple clinical and laboratory variables which may be under-recognized by the treating physicians, leading to an observed risk-treatment paradox in the use of invasive and pharmacological therapies. The routine application of established clinical risk scores, such as the Global Registry of Acute Coronary Events risk score, is recommended by major international clinical practice guidelines for structured risk stratification at the time of presentation, but uptake remains inconsistent. This article discusses the methodology of designing, deriving, and validating clinical risk scores, reviews the major validated risk scores for assessing prognosis in ACS, and examines their role in guiding clinical decision-making in ACS management, especially the timing of invasive coronary angiography. We also discuss emerging data on the impact of the routine use of such risk scores on patient management and clinical outcomes, as well as future directions for investigation in this field.