Cyclin-dependent kinase 5 (Cdk5) has been previously 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 the accumulating research on the role of Cdk5 in the regulation of 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 may contribute to Cdk5’s action in regulating embryonic and adult neurogenesis, stressing future research directions that will help clarify the mechanisms underlying lifelong neurogenesis in the mammalian brain.