Cell-mediated suppression of anti-tumor immunity is multifactorial in patients with cancer, and recent studies have focused on several distinct cellular agents that are associated with this phenomenon. This review will focus on the potential role of regulatory T cells (Tregs) and microglia in the suppression of cellular immunity observed in patients with glioblastoma. We discuss the ontogeny, basic biology, evidence for activity, and potential clinical options for targeting Tregs and microglia as part of immunotherapy in affected patients.