The Foxo subfamily of FOX transcription factors plays a variety of roles in a broad assortment of diverse physiological processes including cellular differentiation, tumor suppression, metabolism, cell cycle arrest, cell death and protection from stress. Animal models have proved to be invaluable tools in furthering our understanding of the role of particular genes in complex organismal processes. Multiple animal models in diverse species, including Caenorhabditis elegans, Drosophila. melanogaster and the laboratory mouse, exist for the Foxo family of transcription factors. Foxo genes are highly conserved throughout the evolution and each of these model systems has provided valuable insight into the roles of Foxo factors. Many roles are conserved among the different model organisms. Several Foxo-related animal model systems are reviewed here along with the knowledge gleaned to date from each model system.