Patient tolerability of adverse effects is integral to successful treatment. Although standard antiepileptic drugs (AEDs) are well tolerated by many patients, the promise of newer AEDs has been the potential for diminished burden of problems with similar seizure control. This report reviews the prevalence of systemic and neurological adverse effects reported in clinical trials of AED monotherapy. A central finding in this report was the unidirectional higher prevalence of selected adverse effects from standard compared with newer AEDs. A system of questioning every patient at every visit to elicit information may be helpful when balancing benefit-to-risk ratio of individualized therapy during everyday practice.