Epileptic seizures are associated with significant morbidity, impaired quality of life, mortality and substantial healthcare costs. Treatment with anti-epileptic drugs is the mainstay of therapy, with pharmacotherapy aiming to achieve seizure freedom or seizure reduction. Given that approximately 30% of patients are not controlled with monotherapy regimens, adjunctive therapy with multiple anti-epileptic drugs can be envisaged. This article aims to review economic evaluations of anti-epileptic drugs as adjunctive therapy for refractory epilepsy in adult patients. Studies were included if they examined the costs and consequences of different pharmacotherapeutic adjunctive therapies for refractory epilepsy. Uncertainty surrounds the cost-effectiveness of anti-epileptic drugs as adjunctive therapy for refractory epilepsy owing to methodological limitations and design differences between studies. Although cost-effectiveness estimates vary between studies, adjunctive therapy of refractory epilepsy appears to be cost effective, depending on the cost-effectiveness threshold used by pricing/reimbursement agencies. However, there is a need for more, better-designed and comprehensive economic evaluations of adjunctive therapy for refractory epilepsy with anti-epileptic drugs.