The article discusses cellular defenses against superoxide and hydrogen peroxide, focusing on mechanisms and responses in bacteria. It highlights that life evolved in an anaerobic world, and after the appearance of photosystem II, oxygen levels rose slowly, leading to the development of defenses against reactive oxygen species (ROS). Contemporary organisms have inherited these defenses, and bacteria are an accessible model for studying them. The review covers recent developments and remaining puzzles in understanding oxidative stress. Key mechanisms include the formation of ROS, which are byproducts of aerobic metabolism. Superoxide (O₂⁻) and hydrogen peroxide (H₂O₂) are reactive and can damage biomolecules, particularly iron-sulfur clusters. Bacteria have evolved scavenging enzymes like superoxide dismutase (SOD) and catalases to neutralize these species. Additionally, inducible responses, such as the SoxR(S) and OxyR/PerR regulons, help cells adapt to oxidative stress. The article also discusses the role of iron in oxidative stress, noting that unincorporated iron can generate hydroxyl radicals, which are highly damaging. Iron homeostasis is controlled by Fur protein, which regulates iron import and export. Mutations in Fur can lead to increased mutagenesis and sensitivity to oxidative stress. The text explores how bacteria manage oxidative stress through various mechanisms, including the repair of damaged proteins, DNA repair systems, and the regulation of iron levels. It also addresses the role of manganese in protecting against oxidative stress, as manganese can scavenge both superoxide and hydrogen peroxide. However, the exact mechanisms and the role of non-enzymatic systems in catalyzing these reactions remain areas of ongoing research. The review emphasizes the importance of understanding these defenses for both basic science and potential applications in biotechnology and medicine.The article discusses cellular defenses against superoxide and hydrogen peroxide, focusing on mechanisms and responses in bacteria. It highlights that life evolved in an anaerobic world, and after the appearance of photosystem II, oxygen levels rose slowly, leading to the development of defenses against reactive oxygen species (ROS). Contemporary organisms have inherited these defenses, and bacteria are an accessible model for studying them. The review covers recent developments and remaining puzzles in understanding oxidative stress. Key mechanisms include the formation of ROS, which are byproducts of aerobic metabolism. Superoxide (O₂⁻) and hydrogen peroxide (H₂O₂) are reactive and can damage biomolecules, particularly iron-sulfur clusters. Bacteria have evolved scavenging enzymes like superoxide dismutase (SOD) and catalases to neutralize these species. Additionally, inducible responses, such as the SoxR(S) and OxyR/PerR regulons, help cells adapt to oxidative stress. The article also discusses the role of iron in oxidative stress, noting that unincorporated iron can generate hydroxyl radicals, which are highly damaging. Iron homeostasis is controlled by Fur protein, which regulates iron import and export. Mutations in Fur can lead to increased mutagenesis and sensitivity to oxidative stress. The text explores how bacteria manage oxidative stress through various mechanisms, including the repair of damaged proteins, DNA repair systems, and the regulation of iron levels. It also addresses the role of manganese in protecting against oxidative stress, as manganese can scavenge both superoxide and hydrogen peroxide. However, the exact mechanisms and the role of non-enzymatic systems in catalyzing these reactions remain areas of ongoing research. The review emphasizes the importance of understanding these defenses for both basic science and potential applications in biotechnology and medicine.