Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) has made it possible to study the individual variations in drug utilization, to reveal noncompliance in patients and for quality assurance aspects. Even if there is a shortage of data from randomized controlled studies concerning the effectiveness of using TDM as an aid to dosage adjustment, experience from nonrandomized investigations and long-lasting clinical experience have shown that TDM of both older and newer AEDs may be of clinical benefit if used appropriately. The main situations for TDM include: after starting treatment to provide a baseline steady-state concentration for further evaluation of an individual therapeutic concentration; after change in drug dosage, in particular when nonlinear kinetics apply; at therapeutic failure to sort out a pharmacokinetic explanation for uncontrolled seizures or side effects; in case of drug interactions; and when pharmacokinetic changes due to physiological or pathological changes are foreseen (e.g., age-dependent conditions [children, elderly], pregnancy, hepatic disease, renal disease or gastrointestinal conditions potentially affecting drug absorption) and change in drug formulation (brand name/generic). Recently, new terminology and definitions have been suggested by the International League Against Epilepsy. The reference range is a range of drug concentrations quoted by laboratories and is not a therapeutic range. Emphasis should be placed on the concept of an individual therapeutic concentration.