Psychosis, irritability, and aggression in persons with epilepsy are frequently the focus of clinical intervention. These neuropsychiatric symptoms may occur due to the bidirectional relationship between psychosis and epilepsy, in which the potential etiopathogenic mechanisms are believed to be closely related to the seizure disorder itself and also may result from underlying brain injury or behavioral intolerance of antiepileptic or other medication. Epileptic patients are at heightened risk for mood disorders, psychotic disorders, and delerium. The possible lowering of seizure threshold by psychotropic drugs should not contraindicate appropriate use of psychotropic agents, and risk may be minimized by the selection of agents not associated with a relatively high likelihood of altering seizure threshold. Behavioral toxicity of antiepileptic drugs (AEDs) is addressed by selection of alternative agents, and some AEDs appear to possess positive psychotropic effects. The use of antipsychotic, antidepressant, and other psychotropic agents in psychosis, irritability, and aggression in epilepsy is discussed, including dosage ranges, major side effects, and potential interactions between antieplieptic and psychotropic medication.