The Forkhead Box subgroup O (FoxO) transcription factor family is one of the most important downstream targets of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway playing an important role in many biological functions including transcriptional regulation of cellular differentiation. Neuronal differentiation is a complex process which involves many signaling pathways and molecular mechanisms. Interestingly, recent studies indicate that the FoxO family is involved in a number of signaling pathways regulating cell differentiation. The actions occur at different stages in the differentiation process and by differing mechanisms. This review will focus on FoxO as a novel transcription factor in neural differentiation.