Abstract: As the tumor cell-centered treatment strategies cannot curb the malignant progression of glioblastoma effectively, the therapeutic effect of glioblastoma is still not satisfactory. In addition to glioma cells, glioma microenvironment (GME) comprises massive numbers of non-tumor cells and soluble cytokines. The non-tumor cells include endothelial cells, pericytes, microglia/macrophages, mesenchymal cells, astrocytes, neurons, etc. These non-tumor cell components, together with glioma cells, form one organism which regulates the progression of glioma. Considerable progress has been been in research on GME, which will be conducive to the development of non-tumor cell targeted therapies and and improvements in the prognosis of glioma patients. Herein, we summarized the interaction of glioma cells with endothelial cells, pericytes, microglia/macrophages, astrocytes, neurons and mesenchymal cells, a topic that has been extensively researched, as well as the corresponding translational studies. We also discussed the potential challenges and opportunities of developing glioma treatments based on tumor microenvironment.