Background While there are many reports of radiosurgery for treatment of drug-resistant epilepsy, a literature review is lacking. Objective The aim of this systematic review is to summarize current literature on the use of stereotactic radiosurgery (RS) for treatment of epilepsy. Methods Literature search was performed using various combinations of the search terms “radiosurgery” “stereotactic radiosurgery” “Gamma Knife” “epilepsy” and “seizure” from 1990 until October 2015. Level of evidence was assessed according to the PRISMA guidelines. Results Fifty-five articles fulfilled inclusion criteria. Level 2 evidence (prospective studies) was available for the clinical indications of mesial temporal lobe epilepsy (MTLE) and hypothalamic hamartoma (HH) treated by Gamma Knife (GK) RS. For remaining indications including corpus callosotomy as palliative treatment, epilepsy related to cavernous malformation and extra-temporal epilepsy, only Level 4 data was available (case report, prospective observational study, or retrospective case series). No Level 1 evidence was available. Conclusion Based on level 2 evidence, RS is an efficacious treatment to control seizures in MTLE, possibly resulting in superior neuropsychological outcomes and quality of life metrics in selected subjects compared to microsurgery. RS has a better risk-benefit ratio for small hypothalamic hamartomas compared to surgical methods Delayed therapeutic effect resulting in ongoing seizures is associated with morbidity and mortality risk. Lack of level 1 evidence precludes the formation of guidelines at present.