Heart failure (HF) is a common disorder that is associated with significant mortality and morbidity. However, the diagnosis of HF may at times be difficult when using conventional tools. The cardiac natriuretic peptides, particularly brain (B-type) natriuretic peptide (BNP), have evolved to be useful biomarkers of cardiac function and prognosis in HF and other cardiovascular disorders. Multiple observational studies have established the close association between plasma BNP as well as the N-terminal fragment of the BNP prohormone (NT-proBNP) with the diagnosis of HF and an independent prediction of mortality and HF events. Although there are confounding variables to consider, when used in the correct clinical settings, BNP or NT-proBNP testing can be extremely useful. Furthermore, preliminary data from randomized controlled trials suggest that knowledge of BNP and/or NT-proBNP level may optimize the management of patients with HF. Large-scale randomized controlled trials that evaluate BNP/NT-proBNP-guided therapy are ongoing.