Evolution has selected for sophisticated biochemical mechanisms to maintain a reduced environment in all living cells. Not only is this regulation essential for the numerous biological process within the cell to occur, but it is also the protective mechanism which prevents the many endogenous and exogenous biological oxidations in the cell. However, reactive oxygen species (ROS), which include singlet oxygen (O2); superoxide (O •− 2 ); hydrogen peroxide (H2O2) and lipid peroxides (LOO •), are now increasingly referred to not just as toxic by-products of oxidative stress, but important signalling molecules (second messengers) for the regulation of gene expression [1]. Excess ROS are harmful because they can cause damage to all classes of macromolecules in particular polyunsaturated lipids, proteins and DNA [2]. In this short chapter, we will discuss some of the signal transduction pathways, which can be activated by ROS; the transcriptional regulation of ROS induced genes, and in particular those which repair DNA damage. Many excellent reviews have been published which explore the mechanisms of ROS signalling pathways, but this article will suggest a novel hypothesis outlining how modulation of redox signalling can control the repair of oxidative damage to DNA.