This chapter will focus on the challenges in identifying medication-resistant epilepsy for the common focal and generalized epilepsies in children, adolescents and adults. The encephalopathies of infancy and seizures secondary to single gene mutations have been excluded from consideration, because many of these patients will never attain seizure freedom. Over the years, variations surrounding definitions and strategies across a range of studies in children and adults have complicated the picture and resulted in artificial differences in outcomes across different patient populations studied in various parts of the world using different methodologies. Many of these analyses have been undertaken retrospectively in patients with chronic epilepsy. There has been an increasing awareness of the necessity to follow prospectively only patients with newly diagnosed epilepsy. In 2010, a task force of the International League against Epilepsy (ILAE) published a definition of medication-resistant epilepsy, which has brought some clarity and cohesion to this complex issue [1]. This definition has reduced variation among subsequent studies, helping to clarify questions surrounding population selection, sample size, seizure classification and terminology, and characterization of intractability [2].