The role of autophagy in cancer cell survival and cell death has received much attention in recent years; however, scientists are still trying to unravel the complex relationship that exists between autophagy as a tumor suppressor mechanism and as a promoter of tumor progression. In glioblastoma (GBM), the most fatal tumor of the central nervous system, mounting evidence suggests that autophagy processes are tightly intertwined with GBM tumorigenesis and the development of different molecular subtypes. This has led to exciting prospects that autophagy-targeted therapies may improve the efficacy of conventional therapies as well as therapies targeted at specific genetic alterations in individual GBM patients.