Gliomas, varying in malignancy, account for approximately 80% of all malignant brain tumors, with glioblastoma being diagnosed in over half of these cases. Treating glioblastoma and managing its recurrence remains one of the most significant challenges in oncology. Despite the integration of advanced treatment methods — such as modern microsurgical techniques, chemo-radiation, and targeted therapies — the prognosis for glioblastoma remains poor. Chimeric Antigen Receptor T-cell (CAR-T) therapy, which utilizes genetically modified T-lymphocytes to target tumor-associated antigens, represents a promising new approach to treating glioblastoma. This innovative therapy has the potential to significantly improve patient outcomes and quality of life. However, to date, no CAR-T therapies have been approved for the treatment of solid tumors, including glioblastoma, and most are still in clinical trial phases. The main challenge with CAR-T therapy in solid tumors lies in the difficulty of identifying a universal target antigen due to the intratumoral heterogeneity characteristic of these neoplasms. This article highlights key antigens that serve as targets for CAR-T therapy in brain tumors, including EGFRvIII, B7-H3, IL13Rα2, HER2, and GD2.