The Notch signaling pathway is central to a wide array of developmental processes in a number of organ systems, including hematopoiesis, somitogenesis, vasculogenesis, and neurogenesis. These processes involve maintenance of stem cell self-renewal, proliferation, specification of cell fate or differentiation, and apoptosis. Recent studies have led to the recognition of the role of the Notch pathway in early neurodevelopment, learning, and memory, as well as late-life neurodegeneration. This review summarizes what is currently known about the role of the Notch pathway in neural stem cells, gliogenesis, learning and memory, and neurologic disease.