Worldwide 70  million people suffer from epilepsy, a chronic neurological disorder characterized by recurrent seizures. Antiseizure medications are the first-line treatment, but despite the continuously increasing number of available drugs, 30% of patients do not achieve long-term seizure freedom. In addition, many patients suffer from drug-related side effects, further highlighting the need for alternative therapies. The development of more efficacious novel therapies, however, is impeded by incomplete knowledge on the complex pathophysiology of epilepsy, including diverse mechanisms such as network reorganization and neuroinflammation. Furthermore, it is incompletely understood how emerging neuromodulation treatments interact with normal and epileptogenic networks. The aim of our translational research in both rodents and epilepsy patients is to address these gaps, eventually resulting into rational, more efficacious and better tolerated treatments in drug-resistant epilepsy.