OBJECTIVE: Despite recent advances in neurosurgical resection techniques, radiation therapy, and chemotherapy, malignant gliomas continue to have a dismal prognosis because relapses are unavoidable. METHODS: Dendritic cell vaccination has recently emerged as a promising type of active immunotherapy that aims to induce rather than transfer specific antitumor immune responses in patients. Active immunotherapy is the only type of immunotherapy able to induce immunological memory. RESULTS: Although an increasing number of small clinical trials show safety, feasibility, and immunological and clinical responses, this technology requires further clarification of some critical basic and clinical issues before its presumed place in the treatment of malignant gliomas can be specified. This article addresses the basic and clinical pitfalls that, more than with conventional therapies, may interfere with the potential benefits of this approach. CONCLUSION: Considering the particular mechanisms involved in the immune modulation of tumor biology using dendritic cell-based vaccinations, the authors summarize the arguments in favor of a further, appropriate assessment of this technology.