Extracellular signals dictate the biological processes of neural stem cells (NSCs) both in vivo and in vitro. The intracellular response elicited by these signals is dependent on the context in which the signal is received, which in turn is decided by previous and concurrent signals impinging on the cell. A synthesis of signaling pathways that control proliferation, survival, and differentiation of NSCs in vivo and in vitro will lead to a better understanding of their biology, and will also permit more precise and reproducible manipulation of these cells to particular end points. In this review we summarize the known signals that cause proliferation, survival, and differentiation in mammalian NSCs.