Malignant gliomas are characterized by its invasiveness and dissemination, resulting in frequent tumor recurrence after surgical resection and/or conventional chemotherapy and radiation therapy. Various strategies of active and passive immunotherapy in developing stages have shown promise to increase patient survival time with little severe side effects. In recent years, glioma stem cells had been isolated from patient tumor specimens. Biochemical and biological characterization of these cancer initiating cells implicated their critical roles in cancer growth, malignancy and resistance to conventional treatments. In this chapter, we review recent research progress in targeting brain cancer using neural stem cells delivered cytotoxic factors and immune regulation factor, dendritic cell based vaccination, with special emphasis on targeting glioma stem cells. We present evidence supporting the notion that glioma stem cells may be preferred therapeutic targets not only for conventional therapies, but also for immunotherapies. Future progress in glioma stem cell research may fundamentally improve the prospect of malignant glioma treatments.