Embryonic stem (ES) cells are a unique resource, providing in principle access to unlimited quantities of every cell type in vitro. They constitute an accessible system for modeling fundamental developmental processes, such as cell fate choice, commitment, and differentiation. Furthermore, the pluripotency of ES cells opens up opportunities for use of human ES cells as a source of material for pharmaceutical screening and cell-based transplantation therapies. Widespread application of ES cell-based technologies in both basic biology and medicine necessitates development of robust and reliable protocols for controlling self-renewal and differentiation in the laboratory. This chapter describes protocols that enable the conversion of mouse ES cells in simple adherent conditions to either terminally differentiated neurons and glia or self-renewing but lineage-restricted neural stem cell lines. It also reports on the current status in transfer of these approaches to human ES cells.