It is important to correctly diagnose medically intractable epilepsy in children and to identify those children whose medically refractory, localization-related seizures may be surgically remediable as soon as possible to optimize the surgical outcome. In this paper the authors review the definition of medically intractable seizures and discuss the various causes and risk factors for this disorder in children. They also outline the presurgical diagnostic evaluation process for pharmacologically intractable epilepsy in children who may be candidates for surgical treatment of localization-related seizures. The treatment of children with medically intractable epilepsy is both challenging and rewarding. Surgery has the potential of altering the natural history of epilepsy by improving or eliminating seizures in carefully selected patients.