Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Testing for natriuretic peptide markers, such as B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP), has emerged as an important tool for the diagnosis and risk stratification of patients with HF. However, questions remain regarding the potential role for natriuretic peptides to guide therapy in patients with HF. In this Review, we address the underlying assumptions and the existing evidence supporting a natriuretic-peptide-guided approach to the outpatient management of HF.