Abstract: Glioblastoma is the most common and devastating primary brain tumor, with only 15-19 months. It has been confirmed that glioma stem cells (GSCs) is one type of cancer stem cells in malignant glioma showing the abilities of self-renewal, unlimited proliferation and multi-directional differentiation of neural stem-like cells. GSCs may play a critical role in the resistance to conventional treatment and tumor relapse. The microenvironment, composed of interstitial cells and body fluid components, regulates the proliferation, differentiation, apoptosis, drug resistance and other mechanisms in GSCs. It does necessarily affect the characteristics of stem cells and tumor malignant phenotype. In recent years, significant progress has been made, opening new avenues in investigating the mechanisms of growth, invasion and migration of glioma and its interaction with microenvironment. This review focuses on the impact of microenvironment including abnormal vasculature, hypoxia and immunosuppression on GSCs, and its potential therapeutic targets for selective inhibition of GSCs.