The advent of O2 in the atmosphere was among the first major pollution events occurred on earth. The reaction between ferrous iron, very abundant in the reductive early atmosphere, and oxygen results in the formation of harmful superoxide and hydroxyl radicals, which affect all macromolecules (DNA, lipids and proteins). Living organisms have to build up mechanisms to protect themselves against oxidative stress, with enzymes such as catalase and superoxide dismutase, small proteins like thioredoxin and glutaredoxin, and molecules such as glutathione. Bacterial genetic responses to oxidative stress are controlled by two major transcriptional regulators (OxyR and SoxRS). This paper reviews major key points in the generation of reactive oxygen species in bacteria, defense mechanisms and genetic responses to oxidative stress. Special attention is paid to the oxidative damage to proteins.