There is considerable interest and debate concerning the place of generic substitution, especially relating to antiepileptic drugs (AEDs). Sadly, one of the causes of the ongoing debate is confusion, often intentionally fueled by the pharmaceutical industry among health professionals and patients regarding the regulatory determination of bioequivalence. Few understand the correct definition. It is often erroneously stated that to be considered bioequivalent there is an allowed difference in the extent and rate of absorption of 80% to 125% between a generic drug product and the branded standard. This is false and implies that there is a wide leniency allowed, with varying clinical outcomes probable. This myth needs to be countered to ensure the safety of patients. A balanced review of the issues surrounding the generic substitution of AEDs is presented.