The reduction of NO center dot to HNO/NO- under biologically compatible conditions has always been thought as unlikely, mostly because of the negative reduction potential: E degrees (NO center dot,H+/HNO) = -0.55 V vs NHE at physiological pH. Nonetheless, during the past decade, several works hinted at the possible NO-to-HNO conversion mediated by moderate biological reductants. Very recently, we have shown that the reaction of NO center dot with ascorbate and aromatic alcohols occurs through a proton-coupled nudeophilic attack (PCNA) of the alcohol to NO center dot, yielding an intermediate RO-N(H)O-center dot species, which further decomposes to release HNO. For the present work, we decided to inspect whether other common biological aromatic alcohols obtained from foods, such as Vitamin E, or used as over-the-counter drugs, like aspirin, are able to undergo the reaction. The positive results suggest that the conversion of NO to HNO could occur far more commonly than previously expected. Taking these as the starting point, we set to review our and other groups' previous reports on the possible NO-to-HNO conversion mediated by biological compounds including phenolic drugs and vitamins, as well as several thiol-bearing compounds. Analysis of revised data prompted us to ask ourselves the following key questions: What are the most likely physio/pathological conditions for NO center dot-to-HNO conversion to take place? Which effects usually attributed to NO center dot are indeed mediated by HNO? These inquiries are discussed in the context of 2 decades of NO and HNO research.