Cyclin-dependent kinase 5 (Cdk5) has been implicated in the migration, maturation and survival of neurons born during embryonic development. New evidence suggests that Cdk5 has comparable but also distinct functions in adult neurogenesis. Here we summarize accumulating evidence on the role of Cdk5 in regulation of the cell cycle, migration, survival, maturation and neuronal integration. We specifically highlight the many similarities and few tantalizing differences in the roles of Cdk5 in the embryonic and adult brain. We discuss the signaling pathways that might contribute to Cdk5 action in regulating embryonic and adult neurogenesis, highlighting future research directions that will help to clarify the mechanisms underlying lifelong neurogenesis in the mammalian brain.