The objective of this study was to investigate the association between natriuretic peptides, obesity and related comorbidities. A systematic review of the English language literature from 1996 to 2008 was performed with Pubmed/MEDLINE and the ISI Web of Knowledge. ‘Natriuretic peptides’, ‘atrial natriuretic factor’, ‘brain natriuretic peptide’, ‘obesity’, ‘body mass index’, ‘lipolysis’ and ‘adipose tissue’ were used as Mesh terms. We also conducted a handle search among the references of the original articles selected. Finally, seventy-five studies were considered eligible for inclusion in the review. Natriuretic peptides are widely known as body homeostasis regulators. Recently, their action as lipolytic agents has been identified. Obese patients, especially those with hypertension and metabolic risk factors, have reduced plasma levels of natriuretic peptides. Whether this precedes or follows obesity and its complications remains undefined. The lipolytic effect of natriuretic peptides indicates that they may be involved in the pathophysiology of obesity. In general, studies with obese patients support paradoxical reduced levels of natriuretic peptides. However, the selection of subjects and classification of obesity and heart failure varied among the reviewed studies, rendering comparison unreliable.