Glioblastoma multiforme (GBM) is the most malignant form of brain tumors. Despite intensive treatment, the mean survival of these patients is about 1 year. Recent studies have shown that a small population of cells, called brain tumor stem cells, are resistant to chemo- and radiotherapy. They thus have the ability to reinitiate the tumor. Therefore, it seems that destroying these cells is very important for curing this disease. This review summarized the methods for isolating and enriching brain tumor stem cells. It also discussed critical signaling pathways and transcription factors that are important targets for new drugs. Keywords: Glioblastoma multiforme, Neural stem cells, Brain tumor stem cells, Brain tumor