Advances in clinical care for disorders involving any system of the body 
necessitates novel therapeutic strategies that can focus upon the modulation of 
cellular proliferation, metabolism, inflammation and longevity. In this respect, 
members of the mammalian forkhead transcription factors of the O class (FoxOs) 
that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as 
exciting prospects for multiple disorders. These transcription factors govern 
development, proliferation, survival and longevity during multiple cellular 
environments that can involve oxidative stress. Furthermore, these transcription 
factors are closely integrated with several novel signal transduction pathways, 
such as erythropoietin and Wnt proteins, that may influence the ability of FoxOs 
to act as a "double-edge sword" to sometimes promote cell survival, but at other 
times lead to cell injury. Here we discuss the fascinating but complex role of 
FoxOs during cellular injury and oxidative stress, progenitor cell development, 
fertility, angiogenesis, cardiovascular function, cellular metabolism and 
diabetes, cell longevity, immune surveillance and cancer.