BACKGROUND: The clinical and economic consequences of generic antiepileptic drug (AED) substitution are not yet fully understood. This article provides a broad perspective of generic AED substitution in five countries. METHODS: Two cross-sectional telephone-based surveys (patient and physician) were undertaken in Canada, the United Kingdom, France, Germany, and Spain. A total of 1409 interviews, 974 patients and 435 physicians, were completed. RESULTS: Across all countries studied, patients and physicians alike have elevated concerns about the safety and efficacy of generic AEDs as compared with drugs for acute care. CONCLUSION: There is an opposition to generic substitution by both patients and physicians, especially with concern over increased breakthrough seizure risk. Further evidence is required to understand how costs and effects of generic AED substitution affect patient welfare.