Biomarkers, particularly natriuretic peptides (NP), complement clinical assessment in patients with heart failure (HF) and may serve as a target level to aid titration of treatment. NP levels that decrease with treatment for acute HF may identify patients at lower risk, but irrespective of the decrease, higher levels at discharge still portend worse outcomes. Beyond NPs, other biomarkers including ST2 have been shown to provide incremental value for prognosis. Although presentation ST2 values are prognostic, admission to discharge change in ST2 and the final ST2 concentration both independently predict patient outcomes in a stronger fashion. Although prognostic thresholds in the hospitalized patient are considerably higher than those used in the office-based setting, a minimum ST2 value of 35 ng/ml is a reasonable starting point for prognosis, noting that many patients will have considerably higher value than this value; as with the NPs, a decreasing value by discharge is desirable, and lower is always better. In conclusion, ST2 values are complementary to NP concentrations, and one can make a good case for serial testing of both biomarkers in the acutely hospitalized patient with HF.