Abstract Background Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, which can be significantly reduced with anticoagulant treatment. Key goals in the clinical management of AF are the identification of patients at high risk for developing AF and accurate stratification of the risk of stroke and systemic embolic events (S/SEE) as well as treatment-related major bleeding. Content In this review, we describe the expanding evidence regarding the use of circulating biomarkers for predicting the risks of both incident AF and its clinically important complications of S/SEE and treatment-related major bleeding. We also review emerging biomarker-based scores for assessing these risks. Summary Patients with AF undergo progressive cardiac structural remodeling, which may precede the onset of the arrhythmia. Abnormal concentrations of circulating biomarkers reflecting the underlying pathophysiologic mechanisms of hemodynamic stress (i.e., natriuretic peptides), inflammation (i.e., C-reactive protein), and myocardial fibrosis identify patients at higher risk of developing AF. Circulating biomarkers can also be used to identify patients with AF who are at greatest risk for developing S/SEE or major bleeding. In particular, biomarkers of hemodynamic stress, myocardial injury (i.e., cardiac troponin), and coagulation activity (i.e., D-dimer) are key indicators of thromboembolic risk, and cardiac troponin and growth-differentiation factor-15 are strongly associated with risk of anticoagulant-related major bleeding. The biomarker-based age, biomarker, clinical history (ABC)-stroke and ABC-bleeding risk scores improve risk stratification for S/SEE and major bleeding, respectively, when compared with traditional clinical risk scores like the CHA2DS2-VASc and HAS-BLED scores.