ST2, a member of the interleukin-1 receptor family, is a novel biomarker of mechanical stress measurable in serum that has been shown in animal and in vitro models to be physiologically linked to cardiac hypertrophy, fibrosis, and ventricular dysfunction. In patients with acute myocardial infarction and heart failure (HF), an elevated serum level of the soluble isoform of ST2 is associated with an increased risk of mortality or future HF, independent of natriuretic peptides, and correlates with markers of ventricular structure and function. In acute HF, elevated soluble ST2 levels strongly associate with the presence and severity of the disease and forecast short- and long-term mortality independent of other traditional clinical, biochemical, and echocardiographic markers of risk. This review discusses the biology and physiology of ST2, as well as its implications on the pathogenesis and prognosis of patients with acute coronary syndromes or acute and chronic HF syndromes.