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As more patients are diagnosed with heart failure each year, heart failure management has become a growing public health issue. The development of new therapies and effective implementation of existing therapies for heart failure remain a challenge. Biomarkers, such as natriuretic peptides, offer consistent and cost-effective means of monitoring response to therapy. There is growing interest in using biomarkers to guide heart failure therapy due to their objectivity, reproducibility, and accessibility. There have been several trials to date, including the New Zealand Natriuretic Peptide-Guided Heart Failure Therapy study, the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure Studies, the NT-proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death trial, and the Plasma Brain Natriuretic Peptide–Guided Therapy to Improve Outcome in Heart Failure trial, that examined the effectiveness of biomarker-guided heart failure therapy with very promising results. When compared with intensive medical management, natriuretic peptide-guided heart failure therapy was shown to be noninferior in general and slightly superior in certain patient populations. Although larger trials are required to validate their results, these studies have provided evidence for the effectiveness of biomarker-guided heart failure therapy and paved the way for the integration of biomarkers into routine evaluation and management of patients with heart failure. Congest Heart Fail. 2010;16(4)(suppl 1):S62–S67. ©2010 Wiley Periodicals, Inc.