Factors influencing the host immune response to central nervous system (CNS) tumors are not yet well understood. This review will outline what is known about anti-tumor immune responses against CNS tumors and describe how advances in our knowledge of basic immunology may be applied to brain tumor immunotherapy. We will first focus on cellular immune system interactions involved in peripheral anti-tumor immune responses. Then, we will discuss characteristics of tumors arising within the confines of the CNS that distinguish them from peripheral neoplasms, emphasizing immune defects that seem to limit or curtail specific anti-tumor immunity against brain tumors. Finally, the current state of immune-based treatment paradigms and future directions will be discussed, paying particular attention to adoptive cellular immunotherapy and tumor vaccine approaches for the treatment of malignant gliomas.