© AANS, 2015. Object Evidence in support of hemispherectomy stems from a multitude of retrospective studies illustrating individual institutions' experience. A systematic review of this topic, however, is lacking in the literature. Methods A systematic review of hemispherectomy for the treatment of refractory epilepsy available up to October 2013 was performed using the following inclusion criteria: reports of a total of 10 or more patients in the pediatric age group (≤20 years) undergoing hemispherectomy, seizure outcome reported after a minimum follow-up of 1 year after the initial procedure, and description of the type of hemispherectomy. Only the most recent paper from institutions that published multiple papers with overlapping study periods was included. Two reviewers independently applied the inclusion criteria and extracted all the data. Results Twenty-nine studies with a total of 1161 patients met the inclusion criteria. Seizure outcome was available for 1102 patients, and the overall rate of seizure freedom at the last follow-up was 73.4%. Sixteen studies (55.2%) exclusively reported seizure outcomes of a single type of hemispherectomy. There was no statistically significant difference in seizure outcome and type of hemispherectomy (p = 0.737). Underlying etiology was reported for 85.4% of patients with documented seizure outcome, and the overall distribution of acquired, developmental, and progressive etiologies was 30.5%, 40.7%, and 28.8%, respectively. Acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001). Twenty of the 29 studies (69%) reported complications. The overall rate of hydrocephalus requiring CSF diversion was 14%. Mortality within 30 days was 2.2% and was not statistically different between types of hemispherectomy (p = 0.787). Conclusions Hemispherectomy is highly effective for treating refractory epilepsy in the pediatric age group, particularly for acquired and progressive etiologies. While the type of hemispherectomy does not have any influence on seizure outcome, hemispherotomy procedures are associated with a more favorable complication profile.