Dynamic regulation of adult neurogenesis underlies cognitive function, response to therapies, repair of the nervous system, and age-related cognitive deficits. Many agents, including widely used drugs and treatments, can modulate neurogenesis and may potentially ameliorate cognitive impairments associated with age or disease. By developing several novel approaches to investigate division and signaling in neural stem cells we have arrived at a new model of stem cell maintenance and division in the adult brain. This model implies that the disappearance of neural stem cells is a direct consequence of their production new neurons and that the decline of the stem cell pool may be the price paid for the ability to produce new neurons as adults. It also implies that different modes of division and differentiation of stem and progenitor cells may have profound consequences for the cognitive function. Our findings demonstrate that pro-neurogenic therapies may rely on different molecular mechanisms for increasing the production of new hippocampal neurons; however, they also raise awareness of various modes of division and differentiation of stem and progenitor cells having profound long-term consequences for the disease- or age-related changes in the cognitive function.