© 2015 Elsevier Inc. All rights reserved. Biomarkers of cardiovascular diseases are indispensable tools for diagnosis and prognosis, and the use of several biomarkers is now considered the standard of care. New markers continue to be developed, but few prove to be substantially better than established markers. Suppression of tumorigenicity 2 (ST2) is a marker of cardiomyocyte stress and fibrosis that provides incremental value to natriuretic peptides for risk stratification of patients with a wide spectrum of cardiovascular diseases. On the basis of all available data, the 2013 American College of Cardiology and American Heart Association guidelines now recommend measurement of ST2 for additive risk stratification in patients with acute or chronic ambulatory heart failure (HF). This report provides an up-to-date overview of the clinical studies that led to the endorsement of ST2 as a cardiovascular prognostic marker in chronic HF. The presented data suggest that the addition of ST2 to a model that includes established mortality risk factors, including natriuretic peptides, substantially improves the risk stratification for death and HF hospitalization in patients with HF. ST2's prognostic value remains strong even in the subset of patients with renal insufficiency and is superior to other remodeling-fibrosis biomarkers currently being evaluated. In conclusion, these results have been repeatedly validated; thus, ST2 could be rapidly incorporated into clinical practice for risk prediction. Indeed, the body of evidence supporting the use of ST2 in chronic HF stratification continues to grow, with consistent data from cohorts around the world in single-center (Barcelona, Brussels, and San Diego cohorts) and multicenter (Penn Heart Failure Study [PHFS] and Muerte Subita en Insuficiencia Cardiac [MUSIC]) studies and in post hoc studies from clinical trials (Prospective Randomized Amlodipine Survival Evaluation 2 [PRAISE-2], Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION], and Controlled Rosuvastatin Multinational Trial in Heart Failure [CORONA]).