Epilepsy is one of the most common of the serious brain disorders and can occur at all ages. The mainstay of therapy is the use of antiepileptic drugs (AEDs). This chapter first describes translational models that have led to the development of classic AEDs and then addresses novel translational approaches to advance our understanding of areas of high unmet medical need. It describes approaches to identifying and validating targets that are promising in the following areas: antiepileptogenesis, disease modification, pharmacoresistance, genetically determined idiopathic epilepsies, drug utility and drug effectiveness. The drug effectiveness is defined as the (ability to positively influence a variety of common comorbidities, including psychiatric disorders, cognitive impairment, migraine, and neuropathic pain). The chapter explores and drugability or the pharmacokinetic and pharmacodynamic aspects of candidate selection including drug-drug interactions and formulations and delivery options. Animal models have led to a better understanding of the pathology of epilepsy.