Malignant astrocytic gliomas, such as glioblastoma, are the most common and lethal intracranial tumors, characterized by rapid progression, widespread invasion, resistance to treatment, and high mortality. Recent advances in stem cell biology, cell signaling, genome science, and genetic model systems have significantly advanced our understanding of the genetics, biology, and clinical behavior of glioblastoma. This review highlights current challenges and recent scientific advances that promise to improve the clinical management of this devastating disease. Key areas include a comprehensive view of altered genes and pathways, identification of new molecular subtypes, improved understanding of cellular origins and cancer stem cells, refined model systems, and novel therapeutic strategies targeting genetic lesions and pathways. Despite intensive therapeutic strategies, the median survival for glioblastoma remains around 12 months. The review also discusses the classification and grading of gliomas, the biological processes and genetic alterations involved in astrocytic gliomas, and the pathogenesis and treatment of glial tumors, including the role of receptor tyrosine kinases, apoptosis, necrosis, and angiogenesis.Malignant astrocytic gliomas, such as glioblastoma, are the most common and lethal intracranial tumors, characterized by rapid progression, widespread invasion, resistance to treatment, and high mortality. Recent advances in stem cell biology, cell signaling, genome science, and genetic model systems have significantly advanced our understanding of the genetics, biology, and clinical behavior of glioblastoma. This review highlights current challenges and recent scientific advances that promise to improve the clinical management of this devastating disease. Key areas include a comprehensive view of altered genes and pathways, identification of new molecular subtypes, improved understanding of cellular origins and cancer stem cells, refined model systems, and novel therapeutic strategies targeting genetic lesions and pathways. Despite intensive therapeutic strategies, the median survival for glioblastoma remains around 12 months. The review also discusses the classification and grading of gliomas, the biological processes and genetic alterations involved in astrocytic gliomas, and the pathogenesis and treatment of glial tumors, including the role of receptor tyrosine kinases, apoptosis, necrosis, and angiogenesis.