© 2017 Elsevier Inc. All rights reserved. Compared to nitric oxide (NO), S-nitrosothiols (RSNO) are distinct effectors of NO-dependent signaling processes and have been studied from biochemical, biological, and therapeutic perspectives. The formal oxidation states of nitrogen in RSNOs differ by one electron compared to that in NO, a biochemical property that provides unique modes for regulating NO signaling, typically via cysteine posttranslational modification. The past decade has seen significant advances in methods to measure RSNOs and mechanisms governing their metabolism (formation and decay). These will be discussed in this chapter together with perspectives on potential for therapeutics that target endogenous RSNOs, or utilize synthetic RSNOs to regulate NO signaling in various disease states.