Reactive oxygen species (ROS) and reactive nitrogen species (RNS), considered as toxic by-products of aerobic metabolism, play a key role in intracellular signaling pathways. The putative mechanism of cell responses to ROS and RNS is thiol modifications of cysteine residues, which can be oxidized to varying degrees to cause changes in protein conformation and activity. These post-translational modifications include generation of disulphide bridges, formation of sulphenic, sulphinic and sulphonic acids as well as S-glutathionylation and S-nitrosylation. The main feature of these modifications is their potential reversibility (with the exception of sulphonic acid). There is increasing evidence for the involvement of thioredoxins, peroxiredoxins and glutaredoxins in regulation of thiol modifications. This review provides an overview of recent findings and discusses the modifications of protein cysteine residues and their contribution to the maintenance and control of cellular homeostasis.