Radiation-induced cognitive decline in cancer survivors who have received brain radiotherapy is an insidious problem with worsening severity over time. Because of improved survival with modern therapies, an increasing number of long term survivors are affected with limited options for treatment once diagnosed. Recently there has been enthusiasm for evaluating new approaches to prevent the onset of radiation-induced cognitive decline. Clinical trials have assessed the role of pharmaceuticals such as memantine and donepezil in ameliorating the cognitive effects of brain irradiation. Radiosurgery, when clinically appropriate, allows for the avoidance or postponement of whole brain radiotherapy in some patients with brain metastases. Hippocampal-sparing intensity modulated radiotherapy has been proposed as a means of avoiding damage to regions of adult neurogenesis. Finally, cytoprotective agents are being investigated that target the molecular pathways that lead to brain injury and the resultant cognitive decline.