Bacteria have to cope in their natural environment or during bacterial infection in association with the host immune system to reactive oxygen species (ROS) that are known to cause an oxidative stress response and affect the reduced state of the cytoplasm. ROS are produced in microorganisms as the unavoidable consequence of the aerobic life, by incomplete reduction of molecular oxygen during respiration (Imlay, 2003, 2008, 2013). Beside ROS, bacteria have to cope with many other redox-active compounds, including antimicrobials, antibiotics and environmental xenobiotics, which can act as reactive electrophilic species (RES) and affect the cellular redox status (Marnett et al., 2003; Jacobs and Marnett, 2010). ROS and RES cause specific post-translational thiol-modifications in redox-sensing transcription factors which lead to conformational changes and activate or inactive the transcriptional regulator. As consequence, specific detoxification pathways are up-regulated to destroy the reactive species or to repair the resulting damage (Antelmann and Helmann, 2011; Vazquez-Torres, 2012; Imlay, 2013). With the discovery of the peroxide sensor OxyR of Escherichia coli, it became evident that ROS-sensing by thiol-disulfide switches represents an important regulatory device in bacteria (Zheng et al., 1998; Choi et al., 2001; Kim et al., 2002). However, during the last decade this classical thiol-disulfide-switch model for redox regulation has been expanded by different reversible and irreversible thiol-modifications, such as S-thiolation, Cys phosphorylation or thiol-S-alkylation that are employed by thiol-based redox sensors to regulate expression of specific antioxidant enzymes and virulence mechanisms. In addition to thiol-redox switches, redox sensors can also use methionine oxidation switches, His-oxidation or flavin cofactors, iron and iron-sulfur clusters, heme centers either directly or indirectly for redox-sensing. Here, we review the currently known thiol-based ROS, RES and HOCl-specific redox sensors that have been characterized in Gram-positive model bacteria and human pathogens as well as in E. coli.