Glioblastoma (GBM) is the most common and aggressive type of primary brain 
neoplasm. The current standard therapy for GBM consists of maximal surgical 
resection within safe limits, followed by radiation therapy (RT) and 
chemotherapy with temozolomide. Despite advances in treatment, the prognosis of 
GBM remains poor. Epileptic seizure is one of the most common symptoms in 
patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is 
often used as an anti-epileptic drug in patients with brain neoplasms due to its 
effectiveness and low toxicity profile. Several in vivo and in vitro studies 
have indicated that VPA has radiosensitizing effects for gliomas and 
radioprotective influence on normal brain tissue or hippocampal neurons. The 
results of several retrospective studies have also indicated potential benefit 
to improve survival of patients with GBM. Moreover, the promising treatment 
results of a phase 2 trial of concurrent radiation therapy, temozolomide, and 
VPA for patients with GBM have been recently reported. The use of VPA in 
patients with GBM has thus recently receiving more attention. In this article, 
we review the role of VPA in radiation therapy for GBM, focusing on the clinical 
evidence.