The transcription factor FoxO1 plays a central role in the metabolic adaptations to fasting. Furthermore, FoxO1 and its homologs encode enzymes buffering ROS (reactive oxygen species) or repairing damaged DNA, and are involved in stalling the ageing process across evolution. Our recent work conducted in primary cultures of rat hepatocytes suggests new mechanisms by which FoxO1 exerts some of these functions. They revealed an unexpected role for FoxO1 in amplifying metabolic, survival, mitogenic and stress signals, and the existence of multiple feed-back loops by which FoxO1 integrates and controls these pathways. Furthermore, these effects were found to be independent of FoxO1 direct binding to DNA.