The unequivocal demonstration that the carbonate radical (CO(3) (.-)) is produced from the reaction between the ubiquitous carbon dioxide and peroxynitrite, renewed the interest in the pathogenic roles of oxidants derived from the main physiological buffer, the bicarbonate-carbon dioxide pair. Here, we review the biochemical properties of both the carbonate radical and peroxymonocarbonate (HCO(4) (-)), and discuss the evidence of their formation under physiological conditions. Overall, the review emphasizes the recognition of the biological relevance of oxidants derived from the main physiological buffer as a crucial step into the understanding and control of numerous pathological states.