Malignant gliomas, the most common type of primary brain tumor, account for 80% of malignant tumors in the central nervous system (CNS). There are three principal types of glioma: astrocytomas, oligodendrogliomas, and oligoastrocytomas. Glioma stem cells (GSCs) have been found in all types; however, many fundamental questions about GSCs remain unanswered. This review will examine the current state of knowledge regarding GSC origin and the signaling pathways implicated in GSC tumorigenesis. The outstanding challenges for the study of GSCs in the context of glioma progression will also be discussed.