Introduction: A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy. Areas Covered: The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others. Expert Opinion: Several biomarkers have recently been highlighted as ‘risk-enhancing factors’ in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.