Heart failure (HF) is the final common pathway of many cardiovascular diseases and is associated with increased morbidity and mortality. Natural history of HF patients can be improved when early diagnosis is achieved, and a timely treatment is initiated. Circulating biomarkers, reflecting pathophysiological pathways involved in HF development and progression, help clinicians diagnose and manage patients with HF. Natriuretic peptides are cardioprotective hormones released by cardiomyocytes in response to pressure/volume overload. B-type natriuretic peptides, namely B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, have been widely validated as tools for diagnosis and risk stratification of HF, and their use appears promising also for screening the population at risk and as a guide for preventive measures halting progression towards HF. Conversely, there is conflicting evidence regarding their role as a guidance for HF therapy.