Glioblastoma (GBM) is the most frequent and aggressive malignant primary tumor of the central nervous system in adults, with an incidence of 3.23 per 100,000 people. Despite the existence of various therapeutic approaches, the absence of a cure and the unfavorable prognosis persist for this neoplasm, with a median survival of approximately 8-15 months and a 5-year survival rate of 6.9%. In this review, we address the epidemiology, histopathology, molecular characteristics, and treatment of GBM. We highlight the relationship of GBM with the microenvironment in the lateral ventricle wall and the cerebrospinal fluid. The location of GBM in this region results in more aggressive tumors and shorter life expectancy for patients. Understanding the malignancy mechanisms that hinder remission, treatment, and positive prognosis opens the possibility of improving diagnostic and therapeutic interventions against GBM.