Acute encephalopathy with inflammation-mediated status epilepticus, followed by the development of medically refractory epilepsy is a spectrum of disorders being increasingly reported in children. Febrile infection-related epilepsy syndrome (FIRES) occurring in school age children and hemiconvulsions, hemiplegia and epilepsy (HHE) syndrome occurring in younger children are the two most commonly recognized entities. The majority of the affected patients develop medically refractory epilepsy and neurocognitive sequelae. We present two illustrative cases and discuss the difficulties faced in their diagnosis and treatment. No specific etiology has been identified and the diagnosis is often made by exclusion. Ketogenic diet has been shown to be effective in controlling the seizures associated with FIRES. Immunomodulating therapies have shown mixed results. Children with HHE developing refractory epilepsy are potential candidates for epilepsy surgery. Urgent research is needed for identifying novel biomarkers as well as for developing therapies targeted at the inflammatory cascade.