Introduction of O2 to Earth's early biosphere stimulated remarkable evolutionary adaptations, and a wide range of electron acceptors allowed diverse, energy-yielding metabolic pathways. Enzymatic reduction of O2 yielded a several-fold increase in energy production, enabling evolution of multi-cellular animal life. However, utilization of O2 also presented major challenges as O2 and many of its derived reactive oxygen species are highly toxic, possibly impeding multicellular evolution after the Great Oxidation Event. Remarkably, ROS, and especially hydrogen peroxide, seem to play a major (...) part in early diversification and further development of cellular respiration and other oxygenic pathways, thus becoming an intricate part of evolution of complex life. Hence, although harnessing of chemical and thermo-dynamic properties of O2 for aerobic metabolism is generally considered to be an evolutionary milestone, the ability to use ROS for cell signaling and regulation may have been the first true breakthrough in development of complex life. The importance of Earth's oxygen cycle and reactive oxygen species produced on the evolution of complex life. The ability to detoxify oxygen species is not a trait that emerged as a response to increased O2 levels but rather crucial adaptation to the early Earth's weakly oxic microenvironments. (shrink)