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Oxidative stress can have lethal consequences if organisms do not respond and remediate the damage to DNA, proteins and lipids. Bacterial species respond to oxidative stress by activating transcriptional profiles that include biochemical functions to reduce oxidized cellular components, regenerate pools of reducing molecules, and detoxify harmful metabolites. Interestingly, the general stress response in Gram positive bacteria controlled by SigB is induced by oxidative stress from reactive oxygen and electrophilic species. The upregulation of SigB regulated genes during exposure to electrophilic and oxidative compounds suggests SigB contributes directly to the adaptations required for oxidative stress survival. A subset of the functions of SigB regulated genes can be categorized with antioxidant biochemical activities, such as redoxins, reductases and dehydrogenases, including regulation of low molecular weight thiols, yet their exact cellular role is not fully understood. Here, we present an overview of the predicted antioxidant biochemical functions regulated by SigB, with potential for biomedical research given the prevalence of oxidative stress during bacterial infection, as well as during industrial applications of large-scale production of compounds by microbes.