Radiation, surgery, and chemotherapy, singly or combined, are modalities that are frequently used for the treatment of primary brain malignancies and metastases that secondarily spread to the brain. Each of the 3 modalities continues to improve with time; likewise the efficacy in management of malignant brain tumors has gradually improved. As cancer therapies become more effective with regard to disease control and survival, the potential impact of each modality on brain injury, either alone or when combined, becomes even more significant. In addition, with increasing survival, the likelihood of observing long-term injury is likely to increase. Thus, the expression of acute and long-term brain injury is becoming a more important factor in the management of patients with brain malignancies. This review presents current management and investigations associated with these modality-related injuries.