The biology of the natriuretic peptide (NP) system is complex, yet highly phylogenetically preserved. It regulates salt and water handling, promotes vasodilatation, and exerts favorable effects on the heart in the context of processes such as heart failure. Prior assumptions about the production of B-type NP (BNP) and its amino-terminal precursor fragment (NT-proBNP) have recently been refuted. It is now recognized that rather than a 1:1 secretion of these 2 NPs, a mixture of cleaved and uncleaved NPs is released by the cardiomyocyte. It is also recognized that BNP is rapidly modified into a mixture of various fragments. Commercial assays for the detection of BNP and NT-proBNP measure a mixture of cleaved and uncleaved NPs as well as varying amounts of degraded BNP. BNP and NT-proBNP are cleared differentially: BNP is actively removed from the bloodstream and also has passive clearance mechanisms, including renal clearance; NT-proBNP is cleared more passively by organs with high rates of blood flow, including the kidney.