The possibility that natriuretic peptides' effects are important in hypoxia responses of vertebrates is reviewed. Both the transcription and release of natriuretic peptides are affected by oxygen tension. Furthermore, many of the effects observed in hypoxia, such as diuresis and a reduction of plasma volume, are also caused by treatment of the animal with natriuretic peptides. Also, several clinical observations about changes in natriuretic peptide levels in, e.g., sleep apnea and cyanotic congenital heart disease, are consistent with the idea that hypoxia is involved in the etiology of conditions, in which natriuretic peptide levels increase. Virtually all published information on the relationship between oxygen and natriuretic peptides is based on human studies. Because hypoxic conditions are more common in aquatic than terrestrial environments, future studies about the possible role of natriuretic peptides in hypoxia, as well as the role of hypoxia in the evolution of natriuretic peptides, including the different subtypes, should increasingly involve also aquatic organisms.