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Glioblastoma multiforme (GBM), as the most lethal brain tumor, continues to be incurable. Considering the high mortality rate of GBM, it is crucial to develop new treatment approaches. Conventional therapies, including maximal surgical resection, radiation therapy, and chemotherapy (typically temozolomide), have not led to significant changes in the survival rates of GBM patients. However, emerging modalities, such as the use of tyrosine kinase inhibitors, mTOR inhibitors, NF-ΚB modulators, nitrosoureas, and immunotherapeutic agents have shown promising in improving GBM outcomes. In this context, we reviewed the current status of GBM treatment, the efficacy of existing standard therapies in improving disease outcomes, and future therapeutic directions.