Despite the many overall advances in understanding cancer biology and therapeutic development in the last 50 years, most CNS malignancies are still clinically difficult, incurable diseases. Current combinations of aggressive surgical resection, radiation therapy and chemotherapy regimens do not significantly improve long-term patient survival for these cancers. Cancer immunotherapy is a potentially promising new therapeutic strategy that primes a patient's immune system to attack neoplastic cells. We review the preclinical and clinical progress in developing vaccination-based therapy for CNS malignancies to date, including peptide-based vaccinations, dendritic cell-based vaccinations and other potential modalities. Some of the challenges for developing an effective vaccination strategy, such as abnormal immune molecules on glioma cells and abnormal lymphocyte populations within a glioma, are also discussed. © 2009 Adis Data Information BV. All rights reserved.