The three goals of this article are (1) to delineate the limitations in determining the actual incidence of antiepileptic drug (AED) psychiatric and behavioral side effects; (2) to summarize existing data on the direct effects of AEDs on psychiatric and behavioral comorbidities and examine the relationship between these direct effects and specific AED mechanisms of action; and (3) to recognize the indirect effects of AEDs on psychiatric and behavioral medications that can result in aggravation of these comorbidities through drug-drug interactions. All of these data are then combined and formatted into a practical algorithm useful in many clinical situations.