The objective of this review was to overview published cost-of-illness (COI) studies of epilepsy and their methodological approaches. Epilepsy imposes a substantial burden on individuals and society as a whole. The mean prevalence of epilepsy is estimated at 0.52% in Europe, 0.68% in the US, and peaks up to 1.5% in developing countries. Estimation of the economic burden of epilepsy is of pivotal relevance to enable a rational distribution of healthcare resources. This is especially so with the introduction of the newer antiepileptic drugs (AEDs), the marketing of vagal-nerve stimulators and the resurgence of new surgical treatment options, which have the potential to considerably increase the costs of treating epilepsy.A systematic literature review was performed to identify studies that evaluated direct and indirect costs of epilepsy. Using a standardized assessment form, information on the study design, methodological framework and data sources were extracted from each publication and systematically reported. We identified 22 studies worldwide on costs of epilepsy. The majority of the studies reflected the costs of epilepsy in Europe (three studies each for the UK and Italy, one study each for Germany, the Netherlands, Switzerland, France and the EU) and the US (four studies), but studies were also available from India (two), Hong Kong, Oman, Burundi, Chile and Mexico. The studies utilized different frameworks to evaluate costs. All used a bottom-up approach; however, only 12 studies (55%) evaluated direct as well as indirect costs. The range for the mean annual direct costs lay between 40 International Dollar purchasing power parities (PPP-$) in rural Burundi and PPP-$4748 (adjusted to 2006 values) in a German epilepsy centre. Recent studies suggest AEDs are becoming the main contributor to direct costs. The mean indirect costs ranged between 12% and 85% of the total annual costs. Epilepsy is a cost-intensive disorder. A reliable comparison of the different COI studies in epilepsy is not easily feasible, as the evaluated studies show substantial methodological differences with respect to their patient selection criteria, diagnostic stratifications and evaluated costs. Therefore, there is an urgent need for studies that evaluate direct and indirect costs in a standardized fashion.