This chapter illustrates the important issues to consider while shepherding a compound through epilepsy clinical trials. Newer models, such as pilocarpine, kainate, or electrically induced post-status epilepsy models, may be more useful for identifying compounds for treatment resistant epilepsy. Preclinical models are also used to evaluate pharmacokinetic parameters and toxicology. Many drug trials are performed to achieve registration for specific indications by regulatory authorities. Most epilepsy efficacy studies are followed by an open-label extension study. Most studies on antiepileptic drugs have considered children to be less than 12 years, and have included those aged 12 years and over in trials designed primarily for adults. A placebo control is extremely helpful in assessing whether some adverse events are truly related to the intervention being tested, rather than related to the underlying epilepsy.