Heart failure (HF) is a complex syndrome with high mortality and hospitalization rates. Conventional care in patients with HF is usually based on clinical history and physical examination. Natriuretic peptides (NPs), B-type NP (BNP) and N-terminal proBNP, are the gold-standard biomarkers in HF. They are recommended for diagnosing HF, when the physician is uncertain of the diagnosis, and for estimating the prognosis. NPs also guide therapy in HF, as serial NP measurements inform medication adjustments to achieve targets independently of symptoms. In this regard, the data are conflicting. In patients with HF and reduced left ventricular ejection fraction (HFrEF) there is a suggestion that NP-guided therapy is helpful. The studies STARS-BNP and PROTECT demonstrated a reduction in cardiac events with NP-guided therapy. Additionally, mortality in patients aged <75 years reduced in the BATTLESCARRED and TIME-CHF studies, and in a meta-analysis. On the contrary, no differences were observed in the studies PRIMA and GUIDE-IT. In HF with preserved ejection fraction (HFpEF) and in the acute setting, no differences were detected with NP-guided therapy compared with conventional care. In patients at risk of developing HF, NP can be useful to guide therapy and prevent HF. In summary, NP-guided therapy seems to be useful in patients with HFrEF, especially in those aged <75 years, but has no use in HFpEF or in acute HF.