Antiepileptic drugs (AEDs) are no longer restricted to the treatment of epilepsy. These are widely used in a broad spectrum of psychiatric and neurological disorders. Liver plays a major role in the metabolism of a majority of these drugs. Hepatotoxicity is rare, but a real concern when initiating therapy. Likewise, liver disease can adversely affect the biotransformation of some of these drugs. This manuscript addresses the significance of elevated liver enzymes associated with AED use, the role of therapeutic drug monitoring, pharmacokinetics during liver disease and potential risk of hepatotoxicity.