Neural stem/progenitor cells (NSPCs) generate new neurons in the mammalian brain throughout life. Over the past two decades, substantial progress has been made in deciphering the cellular and molecular mechanisms underlying adult neurogenesis and in understanding the role played by new neurons in brain function in animal models of health and disease. By contrast, knowledge regarding the extent and relevance of neurogenesis in the adult human brain remains scant. Here we review new concepts about how new neurons shape adult brain circuits, discuss fundamental, unanswered questions about stem cell-associated neural plasticity, and illustrate how the gap between the animal-based basic research and current efforts to analyze life-long neuronal development of the human brain may be overcome by using novel experimental strategies.