Reactive oxygen species (ROS) are generated continuously in all types of cells as byproducts of the oxygen metabolism. They give rise to the generation of oxidative DNA damage, which is mutagenic and there can initiate carcinogenesis. The relevance of this endogenously formed oxidative DNA damage compared to other types of DNA damage for the overall cancer risk in humans, however, is not yet clear. In the lecture, basic mechanisms of endogenous DNA damage generation and DNA repair will be briefly addressed. Subsequently an approach to assess the contribution of oxidative DNA damage to the spontaneous mutation rates and to the initiation of carcinogenesis will be discussed. In addition, some recent results on the in vivo protection against spontaneous oxidative DNA damage by the phytoalexin resveraterol will be presented.