(Groger M, Radermacher P, Speit G, Muth C-M. Genotoxicity of hyperbaric oxygen and its prevention: what hyperbaric physicians should know. Diving and Hyperbaric Medicine. 2008; 38: 200-205.) Hyperbaric oxygen (HBO) therapy is used for the treatment of a variety of diseases, but also leads to oxidative stress as a result of increased formation of reactive oxygen species. The consequences may be damage to the lung, the central nervous system and the genome. The oxidative attack on DNA causes, among other damage, single and double strand breaks. Using the comet assay, a well-established genotoxicity test, it was possible to show that a single HBO exposure leads to increased levels of DNA strand breaks in a close dose-effect relationship. On the other hand, it was possible. to demonstrate that these strand breaks are repaired rapidly and that, in repeated HBO exposures, DNA strand breaks occur only,after the first treatment, not subsequent ones, indicating an induction of protective mechanisms. In healthy organisms, DNA repair and antioxidant mechanisms maintain a steady-state level of damage with minimal risk to the cell or the whole organism, but it cannot be excluded that HBO might lead to a significant mutational burden in situations where antioxidant defence is deficient or overwhelmed. The administration of antioxidants draws an ambivalent picture; Vitamin C, E or even N-acetylcysteine seems to be ineffective to prevent HBO-induced genotoxicity, whereas the orally effective vegetal superoxide dismutase (SOD, Glisodin (R)) is effective, and, thus, may play a role in the prevention of oxidative DNA damage.