OBJECTIVES: The objective of this literature review was to explore the existing evidences regarding cost-effectiveness of interventions used to treat epilepsy.  METHODS: A systematic literature review was performed using the PICO method: Population was patients suffering from epilepsy; Intervention and Comparators were any treatments, including non-pharmacological treatments, and Outcomes were ICERs. The literature search was performed with the NHS EED filters using MEDLINE, EMBASE and PubMed from January 2005 to May 5th, 2015. RESULTS: The literature review retrieved 5,676 studies of which 19 fulfilled the eligibility criteria. Sixteen articles compared different pharmaceutical therapies and 3 studies compared non-pharmacological treatments to pharmaceutical therapies. Eleven studies included economic evaluations on refractory epilepsy, 4 on Lennox-Gastaut Syndrome and 5 on different epileptic seizure types. Eight were cost-effectiveness analyses, 10 were cost-utility analyses and one presented both. Ten studies compared newer adjunctive antiepileptic drugs (AEDs) to standard therapy alone. Among the various adjunctive AEDs, lacosamide and oxcarbazepine were the most cost-effective AEDs compared to standard therapy alone, with ICERs varying from dominant to (2015US)$47,383/QALY. One study also presented 5 ICERs on newer AEDs used as monotherapy compared to standard therapy and 4 were dominated or subject to extended dominance. Seven studies compared different adjunctive AEDs to each other. Rufinamide was the most studied AED (n=3) and ICERs presented ranged from (2015US)$263,407/QALY to $391,129/QALY when compared to lamotrigine in Lennox-Gastaut syndrome. Among the studies comparing non-pharmacological treatments to standard therapy, the ICERs ranged from (2015US)$4,098/QALY to $117,505/QALY.  CONCLUSIONS: Results suggest that lacosamide and oxcarbazepine are cost-effective adjunctive AEDs compared to standard therapy alone. However, newer AEDs used as monotherapy seem not cost-effective whereas alternative non-pharmacological interventions could be cost-effective compared to standard therapy. This review provides an overview of the cost-effectiveness of treatments in epilepsy and could serve in the realization of future economic evaluations.