Cognitive impairment is the most common comorbid disorder in epilepsy. Several new antiepileptic drugs (AEDs) have been introduced. Several studies have shown retention rate to be the best parameter of the long-term clinical usefulness of a particular drug. Cognitive side effects have been demonstrated to be one of the most important tolerability problems in chronic AED treatment. Randomized clinical trials with monotherapy in patients with newly diagnosed epilepsy represent the most accurate procedure for assessing the cognitive impact of AEDs. Definite evidence for drug-induced cognitive impairment has been established for phenobarbitone (memory impairment), phenytoin (mental slowing), and topiramate (mental slowing and dysphasia). Treatment with these drugs should consider these side effects, and patients should be monitored on a regular basis. Mild effects (mostly psychomotor slowing) were found for carbamazepine, oxcarbazepine, valproate, and lamotrigine (with mild cognitive activating effects). The effects for ethosuximide, tiagabine, gabapentin, levetiracetam, and zonisamide are inconclusive.