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Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Despite advances in surgical resection, radiotherapy and chemotherapy, prognosis remains very poor. Accordingly, recent studies have been focused on the aberrant signal transduction pathways in glioblastoma. Many patient derived primary glioblastomas and cell lines express constitutively activated signal transducers and activators of transcription 3 (STAT3). Here we focused on the recent progresses regarding to the roles of STAT3 in glioblastoma and glioblastoma stem cells (GBM-SCs), the dysregulation of STAT3 in glioblastoma, and targeting STAT3 for glioblastoma therapy.