Glioblastoma (GBM) is the most malignant central nervous system neoplasm and the outcome is difficult to break through for decades. Ninety percent of patients who suffered from treatment failed. Since 2010, the chimeric antigen receptor (CAR)-T cell therapy has achieved a durable effect in the treatment of B-cell hematologic malignancies. Although several preclinical and clinical trials have emerged as a potential option in solid tumor including high-grade gliomas, the results are limited at present. The challenges of CAR-T cells in GBM are including identification of tumor-specific antigens, preservation activity of T cell, trafficking of enough CAR-T cells to the tumor site, and reversed unique immune suppressive environment of the central nervous system. The success of targeting brain tumors with CAR-T cells has more consideration. In this review article, we will summarize the current key clinical trials of CAR-T therapies in this field. And will outline the obstacles of application of CAR-T cells for the treatment of GBM as well. This review is intended to help guide the future direction of CAR-T therapy in GBM that will move the outcome forward in the future.