The measurement of the active hormone of B-type natriuretic peptide (BNP) system actually has several analytical limitations and difficulties in clinical interpretations compared to that of inactive peptide N-terminal proBNP (NT-proBNP) because of the different biochemical and pathophysiological characteristics of two peptides and quality specifications of commercial immunoassay methods used for their measurement. Because of the better analytical characteristics of NT-proBNP immunoassays and the easier pathophysiological and clinical interpretations of variations of NT-proBNP levels in patients with heart failure (HF), some authors claimed to measure the inactive peptide NT-proBNP instead of the active hormone BNP for management of HF patients. The measurement of the active peptide hormone BNP gives different, but complementary, pathophysiological and clinical information compared to inactive NT-proBNP. In particular, the setup of new more sensitive and specific assays for the biologically active peptide BNP1-32 should give better accurate information on circulating natriuretic activity. In conclusion, at present time, clinicians should accurately consider both the clinical setting of patients and the analytical characteristics of BNP and NT-proBNP immunoassays in order to correctly interpret the variations of natriuretic peptides measured by commercially available laboratory methods, especially in patients treated with the new drug class of angiotensin receptor-neprilysin inhibitors.