The FOXO family of transcription factors has been implicated in several cellular processes including cell cycle arrest, cell death and protection from stress stimuli. FOXO function is influenced by multiple signaling pathways. Many of these pathways are known to be misregulated in cancer. Perturbation of FOXO function leads to uncontrolled cell proliferation and accumulation of DNA damage. It is becoming clear that active FOXO proteins play an important role in keeping cells in check and inactivation of FOXO proteins is associated with characteristics of cancer cells. FOXO proteins may represent new therapeutic targets for a broad spectrum of cancers.