Glioblastoma (GBM) is the most common and highly lethal form of primary brain tumor in adults. The median survival of GBM patients is approximately 14–16 months despite multimodal therapies. Emerging evidence has substantiated the critical role of symbiotic interactions between GBM cells and noncancerous immune cells (e.g., myeloid cells and T cells) in regulating tumor progression and therapy resistance. Approaches to target the tumor–immune symbiosis have emerged as a promising therapeutic strategy for GBM. Here, we review the recent developments for pharmacological targeting of the GBM-immune symbiosis and highlight the role of such strategies to improve the effectiveness of immunotherapies in GBM.