Natriuretic peptide has been validated as a useful biomarker in the diagnosis of heart failure, although its role in guiding medical management of heart failure is not well established. We endeavored to determine if natriuretic peptide-guided therapy is associated with improved outcomes for heart failure patients. A total of 11 trials (2628 patients) comparing natriuretic peptide-guided therapy with standard therapy for heart failure patients were identified; follow-up times ranged from 3 months to 3 years. Our data indicate that natriuretic peptide levels and all-cause mortality rates do not appear to benefit from natriuretic peptide-guided therapy when compared with standard therapy. However, a decreased rate of cardiovascular events does appear to be associated with natriuretic peptide-guided therapy.