The view that there are cancer-initiating stem cells has led to a concerted effort to understand the nature of these cells. As in many tissues, rare populations of cancer stem cells have been characterized in neural cancers, including glioblastoma, medulloblastoma and epyndymoma. The ability of stem cells to undergo both symmetric (self-renewal) and asymmetric (division to produce a more differentiated cell) cell division is what defines them as stem cells. Understanding the molecular genetic mechanisms governing the self-renewal and proliferation of these cells will be important in developing novel more effective strategies which will perhaps lead to better treatments for many cancers, including some of the most difficult to treat, such as the most common and aggressive brain cancer, glioblastoma. This review will focus on the molecular genetic mechanisms which have recently been identified as being important for neural stem cell self-renewal in brain cancer.