The goal of epilepsy treatment is no seizures and no side effects. Antiepileptic drugs (AEDs) are the mainstay of treatment. Chronic use, however, often leads to serial drug changes over time, exposing patients with epilepsy (PWE) to recurrent risks due to adverse effects (AEs) and drug interactions. Both unwanted acute and chronic AEs may occur that are usually dose-related, suggested by AED pharmacology, and addressed with appropriate use of serum drug concentrations. Idiosyncratic AEs can pose significant health issues for PWE and be lifesaving with early identification. AED pharmacokinetics and pharmacodynamic properties serve as the foundation for anumber of drug interactions. Hepatic enzyme systems may facilitate AED interaction with other coadministered medication through induction or inhibition of drug metabolism and result in AEs or seizures from drug interactions. A working knowledge of AED pharmacology is an essential component of good clinical practice to help clinicians predict potential AEs and DIs in the treatments of PWE.