Glioblasotmas are the most common primary central nervous system tumor and typically have a dismal prognosis. Immunotherapy has been a promising experimental treatment. Understanding brain tumor immunobiology is critical to designing glioblasotma immunotherapies. In this chapter, we review aspects of basic immunology and neuro-immunology. The antigenic underpinnings of brain tumor immunotherapy including glioma-associated and glioma-specific antigens are discussed. Finally, the molecular and cellular facets of glioma-mediated immunosuppression are outlined. The role of multiple cell types (glioma cells, glioma-infiltrating monocytes, regulatory T cells and myeloid derived suppressor cells) in mediating local and systemic immunosuppression in glioma patients is evaluated.