Perampanel (PER) has been tested in three randomized placebo-controlled prospective phase III trials as an adjunctive antiepileptic drug (AED) in adult and adolescent patients age 12 years and older who had ongoing focal epileptic seizures despite receiving one to three AEDs. Patients were randomized to once-daily placebo or maintenance dosages of 2, 4, or 8 mg of PER daily in one trial or to dosages of 8 and 12 mg of PER in the other two studies. Baseline and double-blind titration periods comprised 6 weeks each before a 12-week maintenance phase. Primary endpoints were median change in partial seizure frequency (baseline vs. double-blind phase), and the percentage of patients achieving >50% reduction in seizure frequency (so-called responders, baseline vs. maintenance). All patients had the opportunity to enter an open follow-up study that allowed a titration of PER of up to 12 mg. Pooled data of all three studies included 1,478 patients. There was a statistically significant median change in seizure frequency and responder rates with PER dosages of 4, 8, and 12 mg (p < 0.01, each dose vs. placebo). Both the results of each trial and the pooled data are reported in this review. For the open follow-up study, 1,218 patients were recruited. Ninety-one percent finally reached maintenance dosages of 10 or 12 mg. After 1 year, both median seizure reduction and responder rates reached almost 50%.