Abstract: Glioma is a refractory intracranial primary malignant tumor.Glioblastoma has the highest degree of malignancy with a very poor prognosis.The standard regimens for the treatment of glioma have reached a plateau with limited benefits for the patients.Over the past two decades, advances in biomarkers and molecular subtyping of major cancers, together with breakthroughs in the development of small molecule compounds and antibody drugs, have ushered in the era of precision medicine for oncotherapy.In the field of glioma treatment, the explosion of clinical trials related to targeted therapy and immunotherapy in recent years has been a milestone, indicating that the precision treatment of glioma has entered a vigorous stage of research and exploration.However, due to the special growth location of glioma and the limited numbers of mutations and neoantigens produced during the disease progression, the exploration of new approaches to the precision treatment of gliomas has encountered more obstacles compared with cancers of other systems.Here, the theoretical basis and clinical trial explorations of precision treatment of glioma are reviewed, and the difficulties encountered in the research and development of precision treatment of glioma are analyzed, with a prospect of the possible solutions and development directions in the future.