Concentrations of both B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) are relatively lower among patients with a higher body mass index (BMI). Based on data at hand, this is probably related to reduced synthesis or secretion of the peptides, rather than increased clearance (which may play only a minor role in this context). Despite this fact, age-adjusted NT-proBNP cut points to "rule in" heart failure (HF) and age-independent cut points to "rule out" HF in patients with acute dyspnea are equally useful for obese and lean patients, and no adjustment of NT-proBNP thresholds for BMI is recommended. Furthermore, the consensus-recommended NT-proBNP cut point of 1,000 ng/L for prognostication in acute dyspnea is equally useful across all BMI categories, without the need for further adjustment for weight. Thus, despite the BMI-related NP handicap observed in overweight and obese patients, NT-proBNP remains powerfully useful for diagnostic and prognostic evaluation across the entire range of BMI values.