The thiol group of cysteine (Cys) residues, often present in the active center of the protein, are of particular importance to protein function which is significantly determined by the redox state of a protein’s environment. Our knowledge of different thiol-based oxidative post-translational modifications (oxiPTMs), which compete for specific protein thiol groups, has increased over the last ten years. The principal oxiPTMs include S-sulfenylation, S-glutathionylation, S-nitrosation, persulfidation, S-cyanylation, and S-acylation. The role of each oxiPTM depends on the redox cellular state, which, in turn, depends on cellular homeostasis under either optimal or stressful conditions. Under these conditions, the metabolism of molecules such as glutathione (GSH), NADPH, nitric oxide (NO), hydrogen sulfide (H2S), and hydrogen peroxide (H2O2) can be altered, exacerbated and, consequently, outside the cell´s control. This review provides a broad overview of these oxiPTMs under physiological and unfavorable conditions, which can regulate the function of target proteins.