The identification of neural stem cells (NSCs) and their contribution to continuous neurogenesis has shown that the hippocampus and olfactory bulb are plastic. Brain plasticity, achieved at the level of cell genesis, has an essential role in the maintenance of brain homeostasis. Via combinatorial functions of extrinsic signals and intrinsic programs, adult neurogenesis is tightly regulated in a specialized microenvironment, a niche. Misregulated neurogenesis is detrimental to normal brain functions and, in extreme cases, pathogenic. Hence, understanding signaling in adult neurogenesis is not only important to understand the physiological roles of neurogenesis, but also to provide knowledge that is essential for developing therapeutic applications using NSCs to intervene in the progression of brain diseases.