One of the most common brain tumors in children and adults is glioma or astrocytoma. There are few effective therapies for these cancers, and patients with malignant glioma fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the past decade, it is now appreciated that these tumors are composed of numerous distinct neoplastic and non-neoplastic cell populations, which could each influence overall tumor biology and response to therapy. Among these noncancerous cell types, monocytes (microglia and macrophages) predominate. In this Review, we discuss the complex interactions involving microglia and macrophages relevant to glioma formation, progression, and response to therapy. Like other cancers, brain tumors (gliomas) are composed of many different cell types, including non-neoplastic monocytic cells (macrophages and microglia). In this Review, Gutmann and Kettenmann discuss the importance of these cells to glioma development, maintenance, and treatment response.