Biomarkers have emerged as indispensable tools for diagnosis and prognostication in a variety of cardiovascular diseases, and several are now standard of care. New markers are constantly being developed, but few are able to significantly improve upon already established markers. ST2 is a marker of cardiomyocyte stress and fibrosis, which provides incremental value to natriuretic peptides for risk stratification of patients across a wide spectrum of cardiovascular diseases. Based upon the totality of data, measurement of ST2 is now recommended for additive risk stratification in patients with acute or ambulatory heart failure in the 2013 American College of Cardiology Foundation and American Heart Association joint guidelines. Looking forward, ST2 levels may be useful for tailoring medical therapy in those with or at risk for developing heart failure. This paper provides an up-to-date overview of the clinical studies that led to the endorsement of ST2 as a cardiovascular prognostic marker, and provides insight into the application of ST2 now and in the future.