Malignant astrocytic gliomas, such as glioblastoma (GBM), are the most common and lethal intracranial tumors. These cancers are characterized by rapid progression, resistance to treatment, and destruction of normal brain tissue. Recent advances in stem cell biology, cell signaling, and genomics have significantly improved understanding of the genetic and biological mechanisms underlying GBM. This review summarizes current challenges and highlights scientific advances that may improve clinical outcomes for GBM patients. GBMs are classified based on histopathological features and clinical presentation. The most common and aggressive type is GBM (WHO grade IV), defined by uncontrolled proliferation, diffuse infiltration, necrosis, and resistance to apoptosis. GBMs exhibit significant intratumoral heterogeneity and are challenging to treat due to their complexity and the presence of cancer stem cells. Despite intensive therapies, the median survival for GBM remains around 12 months. The review discusses the classification and grading of gliomas, emphasizing grade IV GBMs. GBMs are further divided into primary and secondary subtypes, with primary GBMs being more common in older patients and secondary GBMs in younger individuals. Recent genomic studies have revealed distinct molecular profiles between primary and secondary GBMs, highlighting the need for tailored therapeutic approaches. Immunohistochemical markers such as GFAP and OLIG2 are important for classifying gliomas and distinguishing them from non-CNS tumors. New markers are emerging that may aid in the diagnosis and monitoring of gliomas. The review also discusses the role of immunohistochemical markers in predicting clinical outcomes, such as the correlation between PTEN and EGFRvIII expression with response to EGFR inhibitors. The review covers key biological processes and genetic alterations in astrocytic gliomas, including cell cycle dysregulation, mitogenic signaling pathways, and the PI3K/PTEN/AKT pathway. Mutations in genes such as RB, p53, and EGFR are frequently observed in GBMs, contributing to uncontrolled cell proliferation and resistance to apoptosis. The PI3K pathway is often dysregulated in GBMs, and its inhibition is a promising therapeutic strategy. The review also discusses the role of receptor tyrosine kinases (RTKs) in GBM, including EGFR and PDGFR. These receptors are frequently overexpressed or mutated, leading to constitutive activation and promoting tumor growth. Targeting these pathways with inhibitors such as imatinib has shown promise in clinical trials. Apoptosis resistance is a hallmark of GBMs, with genetic alterations in key regulatory molecules contributing to this resistance. The Bcl-2 family of proteins plays a critical role in apoptosis regulation, and their dysregulation is associated with GBM progression. The discovery of Bcl2L12, a potent inhibitor of post-mitochondrial apoptosis, has provided new insights into the molecular basis of necrosis in GBMs. The review highlights the importance of understanding the geneticMalignant astrocytic gliomas, such as glioblastoma (GBM), are the most common and lethal intracranial tumors. These cancers are characterized by rapid progression, resistance to treatment, and destruction of normal brain tissue. Recent advances in stem cell biology, cell signaling, and genomics have significantly improved understanding of the genetic and biological mechanisms underlying GBM. This review summarizes current challenges and highlights scientific advances that may improve clinical outcomes for GBM patients. GBMs are classified based on histopathological features and clinical presentation. The most common and aggressive type is GBM (WHO grade IV), defined by uncontrolled proliferation, diffuse infiltration, necrosis, and resistance to apoptosis. GBMs exhibit significant intratumoral heterogeneity and are challenging to treat due to their complexity and the presence of cancer stem cells. Despite intensive therapies, the median survival for GBM remains around 12 months. The review discusses the classification and grading of gliomas, emphasizing grade IV GBMs. GBMs are further divided into primary and secondary subtypes, with primary GBMs being more common in older patients and secondary GBMs in younger individuals. Recent genomic studies have revealed distinct molecular profiles between primary and secondary GBMs, highlighting the need for tailored therapeutic approaches. Immunohistochemical markers such as GFAP and OLIG2 are important for classifying gliomas and distinguishing them from non-CNS tumors. New markers are emerging that may aid in the diagnosis and monitoring of gliomas. The review also discusses the role of immunohistochemical markers in predicting clinical outcomes, such as the correlation between PTEN and EGFRvIII expression with response to EGFR inhibitors. The review covers key biological processes and genetic alterations in astrocytic gliomas, including cell cycle dysregulation, mitogenic signaling pathways, and the PI3K/PTEN/AKT pathway. Mutations in genes such as RB, p53, and EGFR are frequently observed in GBMs, contributing to uncontrolled cell proliferation and resistance to apoptosis. The PI3K pathway is often dysregulated in GBMs, and its inhibition is a promising therapeutic strategy. The review also discusses the role of receptor tyrosine kinases (RTKs) in GBM, including EGFR and PDGFR. These receptors are frequently overexpressed or mutated, leading to constitutive activation and promoting tumor growth. Targeting these pathways with inhibitors such as imatinib has shown promise in clinical trials. Apoptosis resistance is a hallmark of GBMs, with genetic alterations in key regulatory molecules contributing to this resistance. The Bcl-2 family of proteins plays a critical role in apoptosis regulation, and their dysregulation is associated with GBM progression. The discovery of Bcl2L12, a potent inhibitor of post-mitochondrial apoptosis, has provided new insights into the molecular basis of necrosis in GBMs. The review highlights the importance of understanding the genetic