In the past 20years, many antiepileptic drugs (AEDs) have been marketed that are not significantly metabolized by the liver, but some patients still require the use of older and more metabolically complex AEDs for optimal seizure control, and current economic and insurance-coverage limitations have forced many patients to switch to less expensive agents, which are often the older AEDs. For the patient with hepatic disease, it is clearly preferable to use medications with little potential to exacerbate their condition. In my practice, I try to use agents with simpler metabolism, especially for patients with multiple medical problems. Doing this can mean using AEDs in monotherapy that are FDA-approved only for adjunctive use. I also find that older agents and hepatically metabolized AEDs can be the most appropriate for particular patients. Selection of the optimal seizure medication requires consideration of multiple factors, only one of which is the impact on liver function. I routinely obtain an executive laboratory panel at least yearly for even the healthiest of patients, to reassure both the patient and myself that the metabolism of their AED regimen is not significantly affected. Occasionally, a change or abnormality in liver function is identified. Certainly hepatic disease can make epilepsy management more difficult, and communication between the neurologist and the other treating physicians is a necessity, although the neurologist and the hepatologist may have differing opinions on how to respond to worsening liver function. Concern about potential liver damage by AEDs may prompt unnecessary discontinuation, sometimes with disastrous consequences for seizure control. Overly complex AED regimens can cause underlying liver problems to worsen. Clinical observation and judgment must complement the data derived from laboratory parameters. Worsening hepatic disease can also result in encephalopathic states that worsen or mimic seizures. The EEG can often be helpful in differentiating these conditions and is crucial in determining appropriate epilepsy therapy.