Nitric oxide is a well-known gasotransmitter molecule that covalently docks to sulfhydryl groups of proteins resulting in S-nitrosylation of proteins and nonprotein thiols that serve a variety of cellular processes including cGMP signaling, vasodilatation, neurotransmission, ion-channel modulation, and cardiac signaling. S-nitrosylation is an indispensable modification like phosphorylation that directly regulates the functionality of numerous proteins. However, recently there has been a controversy over the stability of S-nitrosylated proteins (PSNOs) within the cell. It has been argued that PSNOs formed within the cell is a transient intermediate step to more stable disulfide formation and disulfides are the predominant end effector modifications in NO-mediated signaling. The present article accumulates state-of-the-art evidence from numerous research that strongly supports the very existence of How to cite this article: Chatterji A, Sengupta R.