BACKGROUND Historically, radiation oncologists have been cautious about re-irradiating brain tumors because of concerns about the risks of late central nervous system (CNS) toxicity, especially radionecrosis, that may occur several months to years following treatment. Today there are still limited prospective data addressing this approach. MATERIALS AND METHODS Systematic review of published trials reporting clinical results after re-irradiation of patients with different types of brain tumors was performed. RESULTS Data mainly related to glioblastoma, anaplastic glioma, medulloblastoma, ependymoma and meningioma have been published. Randomized studies are scarce. As in first-line scenarios, efficacy of radiotherapy is influenced by histology. Based on the reported outcomes, preliminary recommendations for dose/fractionation regimens can be given. CONCLUSION Re-irradiation of brain tumors is increasingly considered as our understanding of brain tolerance to radiation evolves and developments in radiation technology and imaging make highly accurate targeting of recurrent tumors possible. With developments in systemic therapy, further exploration of the role of re-irradiation on its own or in combination with novel agents is needed.