Glioblastoma (GBM) is a highly aggressive and lethal form of brain tumor in human adults that resists standard of care (SOC) and immunotherapy. Tumor-associated macrophages and microglia (TAMs) represent the most abundant cell population within the GBM tumor microenvironment (TME), comprising up to 50% of the whole tumor mass. TAMs play a pivotal role in promoting tumor progression, driving immunosuppression and inducing therapy resistance. Recent advances have revealed TAM heterogeneity - including their cellular identity (e.g., bone marrow-derived macrophages versus microglia) and the presence of distinct activation/function states and subpopulations within each subtype - in GBM tumors. Targeting the context-dependent TAM infiltration, reprogramming, new subpopulations, survival, phagocytosis, and their interactions with GBM cells in the TME has emerged as a promising therapeutic strategy. Herein we review recent advances in pharmacological targeting of the TAM biology and highlight how these strategies may enhance the effectiveness of SOC and immunotherapies in GBM.