Glioblastoma is the most common brain tumor in adults and is associated with a very low survival rate. The heterogeneity of the tumor microenvironment, its resistance to drug and radiation therapy, and its robust invasiveness all contribute to the poor outcome. Large numbers of glioma associated microglia and macrophages can accumulate within the tumor where they appear to have a role in prognosis. This has stimulated considerable interest in understanding the contribution of these cells to disease progression. Deciphering this biology has been complicated by the fact that these cells are a mixture of brain resident microglia as well as blood-derived macrophages with a spectrum of phenotypes that are likely dependent upon disease stage, tumor location, microenvironment, and perhaps even brain region. Nevertheless, promising preclinical studies suggest that stimulating glioma-associated microglia and macrophages to acquire an M1 anti-tumor phenotype or limiting their recruitment to the tumor microenvironment and the extent of M2 polarization are promising therapeutic strategies for the treatment of glioblastoma. We review not only the heterogeneous contribution of these cells to glioblastoma progression but also recent studies supporting the notion that they are viable therapeutic targets.