To assess the costs of switching from one antiepileptic drug (AED) to another, all associated direct and indirect costs, not only drug acquisition costs, must be considered. The perspective of the healthcare system evaluated in cost-effectiveness analysis is of crucial importance. Multiple clinical factors can influence clinical decisions regarding switching AEDs. The economic cost of poorly controlled epilepsy is enormous and the most cost-effective intervention is an AED that provides total seizure control. Cost-minimisation studies have evaluated costs associated with various medications. If only efficacy and adverse events were considered, then the ‘older’ AEDs were generally more cost effective than the ‘newer’ AEDs. Most studies only examine very specific clinical situations and are not suitable for establishing general clinical recommendations. The pharmacoeconomics of AED choice is highly country specific. While switching to generic formulations is, in general, cost effective, some changes may be detrimental and more costly than remaining on the trade name preparation. For example, as a result of differences in bioavailability and possible loss of seizure control, changing patients to generic phenytoin and carbamazepine can be problematic. Fosphenytoin may only be cost effective in certain clinical situations compared with intravenous phenytoin. Seizure control should not be sacrificed on the basis of costs alone, as the major endpoint in treating epilepsy with AEDs is seizure control without adverse effects. Switching AEDs in clinical practice still depends on the individual clinical situation and choosing AED therapy solely on the basis of initial acquisition costs is unlikely to be cost effective in the long-term care of patients with epilepsy.