This chapter focuses on disorders due to mitochondrial respiratory chain (MRC) dysfunction and use the collective term mitochondrial cytopathy. It discusses two mtDNA disorders, myoclonus epilepsy with ragged red fibers (MERRF) and mitochondrial myopathy encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Epilepsy occurs primarily in the group of patients that develop stroke-like lesions (SLL) and seizures are often preceded by or associated with migraine-like headache. Magnetic resonance spectroscopy can demonstrate elevated lactate in regions of the brain, while positron emission tomography (PET) scanning can provide metabolic information suggesting lowered ATP production. Convulsive status epilepticus (CSE) is treated aggressively using traditional protocols. Benzodiazepine infusion is evaluated as a first line together with phosphenytoin and occasionally phenobarbital. The epilepsies in mitochondrial cytopathies often reveal both focal and generalized features. Treatment of mitochondrial cytopathies comprises awareness of the potential complications and early and aggressive control of seizures.