The Food and Drug Administration requires rigorous testing of generic formulations of antiepileptic drugs to assure bioequivalence to the brand product and asserts that all approved formulations are interchangeable. Physician surveys, case reports, and "switchback" rates from large-scale generic conversions imply that all generic formulations may not be equal to the brand drug for all patient groups. This review presents the current state of the data on bioequivalence and therapeutic equivalence and proposes a series of studies to better clarify the risks of generic formulation substitution in susceptible populations. Until such studies are completed, when switching to generic formulations, health-care providers and people with epilepsy would do well to proceed cautiously and understand the potential risks and benefits of substitution. Extra caution may be needed for patients at highest risk of seizure complications, such as the pregnant patient, patients with recurrent status epilepticus, or patients who have been seizure-free for long periods of time and are driving.