It was well-established that the heart has an endocrine function because it is able to synthesize and secrete a family of related peptide hormones (known as cardiac peptide hormones) with potent diuretic, natriuretic and with complex interactions with the hormonal and nervous systems. Cardiac natriuretic peptides (ANP, BNP, and biologically active peptides of the N-terminal proANP1-98) are differently regulated in their production/secretion patterns and clearance rates; consequently, the assay for these peptides may provide complementary (or even different) pathophysiological and/or clinical information. The assay for cardiac natriuretic peptides has been utilized in clinical conditions associated with expanded fluid volume. In particular, this assay can be useful in discriminating between normal subjects and patients in different stages of heart failure and can also be considered as a prognostic indicator of long-term survival in patients with heart failure and/or after acute myocardial infarction. Non-competitive immunometric assays (such as two-site IRMAs), even if more expensive, seem to be preferable to RIAs for routinary assay of cardiac peptide hormones because they generally have a better degree of sensitivity, accuracy, and precision. The technical characteristics and the potential clinical usefulness of some of the methods for measuring these peptides are reviewed.