Despite significant advances in our understanding of the pathobiology of brain tumors and their treatment, novel therapeutic approaches are urgently needed, particularly for malignant gliomas. In this regard, immunotherapy holds promise and has been a field of intensive research in the last two decades. In order to establish successful immunological strategies, a detailed knowledge of the interaction between brain tumors and the immune system is indispensable. The brain has been called an immunoprivileged site because of a variety of mechanisms that impede the emergence of immune responses. On top of that, brain tumors, most importantly malignant gliomas, elicit pronounced defects in host cell-mediated immunity leading to insufficient immune responses. The activating immune cell ligands that are expressed by tumor cells together with potentially immunogenic antigens are overridden by immune-inhibitory signals with transforming growth factor (TGF)-β as the most prominent immunosuppressive molecule. During the past decade numerous additional molecules and mechanisms have been identified as potential mediators of brain cancer-associated immunosuppression. In contrast, the role of tumor-associated microglia and its antigen-presenting capacity has been clarified only partially, and remains controversial. Only a thorough understanding of these immunological aspects will allow for successful exploitation of the powerful mechanisms of the immune system against brain tumors.