Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can specifically kill tumor cells without damaging normal tissue, has been identifi ed as an ideal gene therapy strategy for glioma. Recent studies revealed that both nanoparticles and stem cells could serve as carriers to improve the delivery effi ciency of TRAIL. In addition, the combination of protease inhibitors, chemotherapy drugs, carbenoxolone sodium, miRNA, PI3-kinase/mTOR inhibitor, and etc, could overcome the glioma resistance to TRAIL and enhance the anti-tumor effect of TRAIL. To sum up, TRAIL shows promising prospects in the treatment of glioma.