Although the brain was traditionally considered as 'immunologically privileged', recent findings have implied an involvement of immune mechanisms in neurological disease and illness, including central nervous system (CNS) malignancies. In this review, we initially focus on aspects of the immune system critical for effective antitumor immunity, as an understanding of normal immunological functions and how they relate to tumor immunology will set a foundation for understanding the unique challenges facing the integration of neuro-oncology and neuroimmunology. We summarize current knowledge of immune responses in the 'immunologically quiescent' brain and its role in tumor immunology. We will then discuss the emerging field of 'immunomics' and recent advances in molecular technologies, such as DNA microarray, which are being applied to brain tumor antigen epitope discovery and patient stratification for brain cancer immunotherapy. This, in turn, should have significant importance for ultimately designing and developing efficient and focused strategies for anticancer immunotherapy. Finally, the current state of immune-based treatment paradigms and future directions will be discussed, paying particular attention to targeted antibody strategies, adoptive cellular immunotherapy, and tumor vaccine approaches that have been studied in clinical trials for CNS neoplasms.