The outcome for glioblastoma patients remains extremely poor, despite the advances in surgical and medical fields. It is hypothesized that glioblastoma progression, as well as tumor recurrence, is driven by a small number of cells called cancer stem cells (CSCs), which are characterized by their ability of self-renewal and proliferation, giving rise to progeny of transformation into multiple neuroepithelial lineages. Understanding the biology of CSCs is likely to explain why existing treatment strategies fail to affect the relatively quiescent and resistant CSC compartment. Here, we review the current knowledge on CSCs in glial tumors. In addition, we discuss the importance of the CSC hypothesis in the advancement of therapies for brain tumors.