The stress-responsive transforming growth factor-ß–related cytokine, growth-differentiation factor-15 (GDF-15), is emerging as a new biomarker in patients with cardiovascular disease. The circulating levels of GDF-15 are elevated and independently related to an adverse prognosis in acute coronary syndrome and left- or right-sided heart failure. GDF-15 adds significant prognostic information to established clinical and biochemical risk markers in these conditions. Elevated levels of GDF-15 may identify patients who have non–ST-elevation acute coronary syndrome who derive the greatest benefit from an invasive treatment strategy. As with other heart failure biomarkers, including BNP, it is currently not known what specific therapies could be used to reduce the risk associated with elevated levels of GDF-15 in heart failure. Further elucidation of the pathobiology and upstream inducers of this new biomarker may lead to new therapeutic concepts that address the risk associated with elevated GDF-15 levels. A commercial assay for GDF-15 should be available in the near future.