The evolutionarily conserved Forkhead box O (FOXO) family of transcription factors regulates multiple transcriptional targets involved in various cellular processes, including proliferation, stress resistance, apoptosis, and metabolism. Target gene regulation appears to be controlled in a cell-type-specific manner due to association of FOXO isoforms with specific cofactors. Many of the cellular processes modulated by FOXO are themselves deregulated in tumorigenesis, and deletion of Foxo genes has demonstrated that these transcription factors function as tumor suppressors. Our understanding of the regulation of FOXO activity, and defining specific transcriptional targets, may provide clues to the molecular mechanisms controlling cell fate decisions. In this review we describe the functional consequences of FOXO activation based on our current knowledge of transcriptional targets.