Glioblastoma multiforme (GBM) is one of the most aggressive types of primary brain tumour. It is characterized by a rapid and drug-resistant progression, high morbidity, and mortality. To survive, GBM cells constitute a genetically heterogenous tumour-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Among these, associated microglia (GAMs) represent the largest population. Once engaged in the TME, microglia acquire a specific activation of the anti-inflammatory and pro-tumour M2 phenotype. On the other hand, “classically activated” microglia usually express the opposite phenotype (M1), with pro-inflammatory and antitumorigenic activity, that is expected to exert a beneficial effect in glioblastoma treatment.