Approximately 30-50% of patients with brain tumors present with seizures as the initial symptom. Seizures play a very important role in the quality of life, particularly in patients with slow-growing primary brain tumors. Tumor-related seizures are often refractory to antiepileptic treatment. Despite the importance of this subject to the fields of neurology, neurosurgery and neurooncology, the pathogenesis of tumor-related epilepsy remains poorly understood. This review summarizes possible mechanisms underlying the pathogenesis of tumor-related epilepsy, including both tumoral and peri-tumoral aspects. Tumor cells themselves may create intrinsic epileptogenicity, and inadequate homeostasis in the peri-tumoral tissues may lead to seizure susceptibility. Other local changes in electrolytes, perfusion, metabolism, and enzymes could also contribute. It is generally accepted that changes in amino acid neurotransmission are the most important mechanism underlying tumor-related seizures, and changes in extracellular ions also play an important role. Hypoxia, acidosis, and metabolic, immunological, and inflammatory changes may also be involved in the occurrence of seizures. Knowledge of these mechanisms may provide guidance in the search for new strategies for the surgical and medical treatment of tumor-related epilepsy. (C) 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.