Objective: To estimate the prevalence of depression in persons with epilepsy (PWE) and the strength of association between these 2 conditions. Methods: The MEDLINE (1948-2012), EMBASE (1980-2012), and PsycINFO (1806-2012) databases, reference lists of retrieved articles, and conference abstracts were searched. Content experts were also consulted. Two independent reviewers screened abstracts and extracted data. For inclusion, studies were population-based, original research, and reported on epilepsy and depression. Estimates of depression prevalence among PWE and of the association between epilepsy and depression (estimated with reported odds ratios [ORs]) are provided. Results: Of 7,106 abstracts screened, 23 articles reported on 14 unique data sources. Nine studies reported on 29,891 PWE who had an overall prevalence of active (current or past-year) depression of 23.1% (95% confidence interval [CI] 20.6%-28.31%). Five of the 14 studies reported on 1,217,024 participants with an overall OR of active depression of 2.77 (95% CI 2.09-3.67) in PWE. For lifetime depression, 4 studies reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1-33.1), and 3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07-4.51) for PWE. Conclusions: Epilepsy was significantly associated with depression and depression was observed to be highly prevalent in PWE. These findings highlight the importance of proper identification and management of depression in PWE.