Refractory epilepsy in veterinary medicine refers to a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional anti-seizure drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. In this session, we discuss the reasons underlying this challenging situation in an individual patient and how this knowledge can help us develop improved therapeutic strategies.