For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis.The authors wish to thank Molly Burhans for preparing the figures. This work was supported by Fundacao para a Ciencia e Tecnologia (FCT) and COMPETE/QREN/EU (PTDC/BIA-MIC/114116/2009), a grant from the Roswell Park Alliance Foundation and by a National Cancer Institute Support Grant (P30CA016056) to Roswell Park Cancer Institute. Authors have no conflict of interest to declare
