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Epilepsy is frequently a severe and sinister symptom in primary mitochondrial diseases, a group of more than 350 different genetic disorders characterized by mitochondrial dysfunction and extreme clinical and biochemical heterogeneity. Mitochondrial epilepsy is notoriously difficult to manage, principally because the vast majority of primary mitochondrial diseases currently lack effective therapies. Treating the underlying mitochondrial disorder is likely to be a more effective strategy than using traditional antiepileptic drugs. This review, initially presented at the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures at the Francis Crick Institute in London, summarizes the currently available and emerging therapies for mitochondrial epilepsy. Potentially treatable mitochondrial diseases include disorders of coenzyme Q 10 biosynthesis and a group of mitochondrial respiratory chain complex I subunit and assembly factor defects that respond to riboflavin (vitamin B2). Approaches that have been adopted in actively recruiting clinical trials include redox modulation, harnessing mitochondrial biogenesis, using rapamycin to target mitophagy, nucleoside supplementation, and gene and cell therapies. Most of the clinical trials are at an early stage (Phase 1 or 2) and none of the currently active trials is specifically targeting mitochondrial epilepsy. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures". • Epilepsy complicates up to 40% of cases of primary mitochondrial diseases. • Mitochondrial epilepsy is extremely difficult to treat. • Ideal therapies should target the underlying mitochondrial disorder. • Many novel therapies are being developed to treat primary mitochondrial diseases. • At least 8 clinical trials are actively recruiting patients. [ABSTRACT FROM AUTHOR]