Cognitive dysfunction associated with both the disease and the adverse effects of radiotherapy (RT) and chemotherapy is a significant problem among brain tumor patients. Currently, it is considered the most frequent complication among long-term survivors. A review of the literature indicates that whole-brain RT alone or in combination with chemotherapy results in cognitive dysfunction more pronounced than from either partial RT or chemotherapy alone. The cognitive domains sensitive to treatment adverse effects include attention, executive functions, memory, and graphomotor speed. An increasing number of studies and clinical trials have incorporated cognitive outcome measures and have provided relevant information about therapy-related neurotoxicity and the incidence of cognitive dysfunction. Recent studies have begun to elucidate the pathophysiologic mechanisms that may underlie RT and chemotherapy injury to the brain. Although there are no established preventive or therapeutic interventions for treatment-induced cognitive dysfunction, this is an area of growing interest, and several approaches are currently under investigation.