The natriuretic peptides are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of actions throughout the body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their volumeregulating effects. These pleiotropic actions include local (autocrine/paracrine) regulatory actions of ANP and BNP within the heart, and of another natriuretic peptide, CNP, within the vessel wall. Effects on function and growth of the local tissue environment are likely to be of great importance, especially in disease states where tissue and circulating levels of ANP and BNP rise markedly. At present, the relevance of other natriuretic peptides (notably uroguanylin and DNP) to human physiology and pathology remain uncertain. Other articles in this issue of Basic Research in Cardiology review the molecular physiology of natriuretic peptide signalling, with a particular emphasis on the lessons from genetically targetted mice; the vascular activity of natriuretic peptides; the regulation and roles of natriuretic peptides in ischaemic myocardium; and the diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart failure.