This chapter reviews some of our knowledge about a specific subgroup of central nervous system (CNS)-related chronic side-effects of antiepileptic drug (AED) treatment, that is, cognitive side-effects: the adverse effects of drug treatment on information-processing systems. Cognitive AED effects may be examined through an analysis of the relationship between test scores of subjects and their individual serum drug levels, and this approach seems to offer a way out of the problem. Although the psychometric studies generally show a tendency of cognitive impairments in polytherapy compared to monotherapy, this merely suggests a drug interaction effect. Systematic analysis of subjective patients complaints about side-effects of AEDs show that the impact of side-effects may be larger than hitherto suspected both in number of patients involved and the frequency of the complaints. Formal psychometric studies are much more difficult to interpret, especially when formal scientific standards in line with evidence-based medicine are applied.