A cost of illness of refractory epilepsy was developed based on estimates supplied by an expert panel of physicians and a review of the current literature. The basic elements of model can be divided into two main components: direct and indirect costs. Direct costs include the medical resource utilization patterns associated with epilepsy care while the indirect costs represent lost productivity associated with the disease. The results of the analysis indicate that an estimated 24,578 incident cases of epilepsy incur a total of $318,582,669; while our prevalence estimates indicate that 335,167 individuals incur a total of $3,905,183,463, in a given year. Direct medical costs account for one-third of the total costs while indirect costs constitute the remaining two-thirds.