This review discusses the management of glioblastoma, a highly aggressive and common malignant brain tumor. It highlights the challenges in treating this disease, including limited effective treatment options and poor prognosis. The review emphasizes the importance of genetic and epigenetic biomarkers in the diagnosis, prognosis, and treatment of glioblastoma. It also discusses recent advances in molecular profiling, which have led to a more refined classification of glioblastoma. Key genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/RAS/PI3K, p53, and retinoblastoma protein (RB) signaling, as well as mutations in isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), and amplification of epidermal growth factor receptor vIII. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. The review also discusses the potential of liquid biopsies in advancing personalized medicine for glioblastoma, highlighting the challenges and promises for the future. The review covers the classification of glioblastoma, molecular pathogenesis, cell signaling pathways, epigenetic mechanisms, and prognostic biomarkers. It also discusses the current treatment options for glioblastoma, including surgery, radiotherapy, and chemotherapy. The review concludes that further research is needed to improve the management of glioblastoma and to develop more effective treatments.This review discusses the management of glioblastoma, a highly aggressive and common malignant brain tumor. It highlights the challenges in treating this disease, including limited effective treatment options and poor prognosis. The review emphasizes the importance of genetic and epigenetic biomarkers in the diagnosis, prognosis, and treatment of glioblastoma. It also discusses recent advances in molecular profiling, which have led to a more refined classification of glioblastoma. Key genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/RAS/PI3K, p53, and retinoblastoma protein (RB) signaling, as well as mutations in isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), and amplification of epidermal growth factor receptor vIII. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. The review also discusses the potential of liquid biopsies in advancing personalized medicine for glioblastoma, highlighting the challenges and promises for the future. The review covers the classification of glioblastoma, molecular pathogenesis, cell signaling pathways, epigenetic mechanisms, and prognostic biomarkers. It also discusses the current treatment options for glioblastoma, including surgery, radiotherapy, and chemotherapy. The review concludes that further research is needed to improve the management of glioblastoma and to develop more effective treatments.