Already established as a powerful nitrating, nitrosating and oxidative agent, peroxynitrite (product of nitric oxide reacting with superoxide radical, ONOO−; PON for short) was clinically ascertained as a potent cell‐death inducer in several devastating diseases. Herein, this clinical evidence is sketched purposely, to emphasize the vital need for PON in vivo detection, as are the strategies employed to develop ONOO− decomposition catalysts as potential therapies. A number of challenges are discussed next, on detecting PON ex vivo or in vivo. While ONOO− optical detection has been available for some time (e.g. oxidation of fluorescent probes, probe nitration, chemiluminescence), these methods tend to be indirect detection methods, elaborate, and rather difficult to apply for real‐time analyses. By contrast, electrochemical quantification of PON appears simpler, more convenient for direct, real‐time, label‐free measurements. Finally, several peroxynitrite‐sensitive interfaces and ways to confer selectivity are examined. However, one needs to be mindful of possible trade‐offs between specificity at a cost of slower response time, especially since ONOO− is a short‐lived species with a 1‐s lifetime. In particular, two recently published, interesting hybrid films are examined: the (hemin‐polythiophene) and the (reduced graphene oxide‐hemin) complex and the apparent significant augmentation in sensor response is further scrutinized.