Recent clinical studies suggest that radiation-induced damage to the hippocampus plays a considerable role in the cognitive dysfunction of patients after cranial irradiation. In particular, deficits in learning, memory, and spatial processing observed in patients who received WBI are thought to be related to hippocampal injury [7]. The mechanisms of radiation-induced cognitive dysfunction are not yet fully understood. According to the available knowledge, radiation-induced cognitive dysfunction is hypothesized to result from dynamic interactions between multiple cell types: vascular and glial clonogens, neurogenesis, neural function and neuroinflammation [8][9][10]. Therefore, studies into the mechanisms and preventive measures of radiation-induced cognitive dysfunction are of paramount importance to decrease the side effects of WBI and increase the quality of life of patients. To achieve this goal, widely acknowledged animal models and universally utilized cognitive tests are the prerequisite and foundation. The Establishment of Rodent ModelsRodents, including mice and rats, are the most commonly utilized animal models in medical research given their genetic background, anatomical structure, operability, and relatively low cost of use [11]. Experimental data indicated that rodents showed similar anatomical AbstractWhole brain irradiation using low LET rays has remained the mainstay to treat some primary and metastatic brain tumors. Radiation-induced cognitive dysfunction is a progressive and irreversible late side effect after whole brain irradiation and inevitably decreases the quality of life of cancer survivors. To address this negative issue, many studies have been performed to explore the mechanisms of radiation-induced cognitive dysfunction and to develop efficacious preventive and treating measures. The prerequisite and foundation of implementing a persuasive and profound study to investigate radiation-induced cognitive dysfunction is the utilization of widely acknowledged animal models and universally applied cognitive tests. In this review, articles studying radiation-induced cognitive dysfunction from 2011 to 2016 were collected. The establishment of animal models and detailed utilization of cognitive tests were analyzed and summarized. This review summarized the general range of irradiation doses and time intervals utilized and the effects of these two factors on the results of cognitive tests. changes and physiopathological mechanisms to human beings after cranial irradiation [12]. In addition, the effects of radiation on rodents could be assessed over relatively short time periods-weeks to months rather than years to decades. Anatomical and functional changes of rodents after cranial irradiation are dependent on age, dose, and sex, which are compatible with the risk factors in human patients [13]. Given that these observations are representative of the effects seen in patients, the rodent model would enable the efficient study of mechanisms and treatments.