OBJECTIVES: The aim of this research is to assess the humanistic and economic burden of focal drug-refractory epilepsy in Europe. METHODS: A PubMed literature review was performed to identify publications from January 2004 to December 2014 on prevalence and incidence, impact on quality of life and associated costs of epilepsy. RESULTS: In Europe around 6 million people have epilepsy, with 30-45% of patients being drug-refractory and 70% of those having focal drug-refractory epilepsy. The prevalence and incidence rate of epilepsy is 457 and 43.87 per 100.000 persons, respectively. Epilepsy is associated with psychiatric comorbidities, chronic somatic conditions, significantly lower quality of life and 2-11 times higher all-cause mortality than the general population. In 2004 health care expenditures for the treatment of epilepsy accounted for 0.2% of the total European national income and the annual cost per patient varied from €2.000 to €11.500. In 2010, the yearly cost of epilepsy ranged from €13.8 to €20 billion. The cost of epilepsy depends on the severity and frequency of seizures and if patients are drug-refractory (20% to 40% of drug-refractory patients account for 80% of the costs). The main cost drivers of epilepsy treatment are hospitalizations, antiepileptic drug costs and indirect costs (due to high unemployment rate; 46% compared with 19% for the matched control population). Standard therapy for drug-refractory focal epilepsy is open surgery which is highly effective but also highly invasive and requires strict screening criteria. Minimally invasive surgical techniques are an alternative to open surgery and have shown promising clinical benefits with lower neurological impairment and less hospital stays compared with open surgery. CONCLUSIONS: This data highlights the high humanistic and economic burden of focal drug-refractory epilepsy in Europe, and the need for new procedures to improve health outcomes and reduce health care resource utilization.