In the span of just 10 years, our understanding of the cancer-immune system relationship has increased exponentially, and yet we are only beginning to understand the intricacies of cytokine and immune cell interactions. This paper reviews the interactions of the immune system with brain tumors. In principle, the immune system is uniquely qualified to be an instrument for cancer therapy. An immune response directed against cells bearing tumor antigens could provide a specific and effective mechanism for killing residual tumor. While the theoretical background for immunotherapy as a treatment for brain tumors is elegant and persuasive, a substantial clinical breakthrough has yet to be made. This paper reviews the major forms of both animal and human data on types of immunotherapy, such as passive serological immunotherapy, active, and adoptive immunotherapy. Next a review of existing data on effects of cytokines, immune regulation, and tumor cytotoxicity is detailed. The review concludes with the clinical trials using interferons and other methodologies. The trials presented here demonstrate the challenging work being done to take basic science into the clinical realm. As this work continues, our ability to design effective immune therapies will mature and yield increased therapeutic success.