Purpose of Review: This review discusses the interpretation of regulatory randomized controlled trials of antiepileptic drugs. An ever increasing number of drugs have been licensed, more so for add-on treatment than for monotherapy. Regulatory trials constitute the main body of evidence to inform clinical decisions about their use. Designs of regulatory trials for monotherapy are the most controversial as regulators take different views as to the type of designs that are required, which has implications for interpretation and for the risks to which patients are exposed., Findings: From the perspective of the regulator, the interpretation of placebo controlled add-on trials is straightforward as they have the capacity to show efficacy compared with placebo. These designs do not, however, inform clinical decisions where a choice among drugs is required. For monotherapy the European Medicines Agency will accept head-to-head trials designed to show noninferiority for licensing. The Food and Drug Administration in the USA will not, and requires trials that show superiority. The resulting 'pseudoplacebo' trials expose patients allocated to pseudoplacebo to risks that may be unacceptable., Summary: Regulatory trials continue to have major limitations for informing clinical decisions and this should be addressed.