Production and release of natriuretic peptides and other vasoactive peptides are tightly regulated in mammalian physiology and involved in cardiovascular homeostasis. As endocrine cells, the cardiac myocytes seem to possess almost all known chemical necessities for translation, post‐translational modifications, and complex peptide proteolysis. In several ways, intracellular granules in the cells contain not only peptides destined for secretion but also important granin molecules involved in maintaining a regulated secretory pathway. In this review, we will highlight the biochemical phenotype of the endocrine heart recapitulating that the cardiac myocytes are capable endocrine cells. Understanding the basal biochemistry of the endocrine heart in producing and se-creting peptides to circulation could lead to new discoveries concerning known peptide products as well as hitherto unidentified cardiac peptide products. In perspective, studies on natriuretic peptides in the heart have shown that the post‐translational phase of gene expression is not only rele-vant for human physiology but may prove implicated also in the development and, perhaps one day, cure of human cardiovascular disease.