Among patients with chronic heart failure (HF), it is known that soluble concentrations of the interleukin receptor family member ST2 (sST2) are prognostic for adverse outcome, including risk for progression of HF and death. Considerably less was known about the merits of serial testing of sST2 and whether such testing provides incremental information beyond single measurements; additionally, the influence of HF therapies on sST2 concentrations and whether sST2 values predicted benefit of therapy changes remained unclear. Recently, several studies indicate that serial testing for sST2 increases the prognostic information gained compared with a single measurement. When measured in patients with chronic HF, concentrations of sST2 appear to predict worsening left ventricular remodeling, and serial measurements of sST2 appear particularly useful for predicting HF events, such as worsening HF and risk for either hospitalization or death from HF. Values for sST2 are lower in those treated with several HF therapies; in turn, sST2 concentrations may predict benefit from specific HF therapy changes. Using an upper reference limit of 35 ng/ml, serial testing for sST2 in chronic HF thus appears useful. The promising role of sST2 for serial chronic HF therapy monitoring will be discussed.