ST2, an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms, was originally described in the context of inflammatory and autoimmune diseases. However, after the identification of IL-33 as the functional ligand for ST2, and conceptualization of the role of ST2/IL-33 signaling in cardiac remodeling, sST2 has emerged as a novel cardiovascular biomarker for the presence of ventricular biomechanical overload. Concentrations of sST2 have been implicated in the presence and severity of heart failure with particular value for prognostication. We will review the use of sST2 as a prognostic marker in heart failure, including present and future directions in this exciting area.