Mitochondria are very important organelles in cells and their main function is to supply the body with energy through oxidative phosphorylation. Structural and functional abnormalities of mitochondria can cause disorders of energy metabolism, especially in organs with high oxygen demand, which are at relatively greater risk of damage. Mitochondrial encephalomyopathies are a heterogeneous group of diseases with multisystem dysfunction caused by defects in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) leading to mitochondrial structure and function. Mitochondrial encephalomyopathies were originally described by Pavlakis and are characterized by mitochondrial myopathy with epilepsy and progressive speech and visual impairment. This clinical syndrome was then confirmed by Hirano and Pavlakis, who defined 3 criteria for mitochondrial encephalomyopathy: (1) stroke-like seizures before age 40; (2) an encephalopathy characterized by epilepsy, dementia, or both; and (3) lactic acidemia, RRF, or both. Most patients have elevated blood lactate levels, electromyography findings of myogenic damage, and imaging may show white matter encephalopathy, basal ganglia calcification, or brain atrophy; blood DNA testing and muscle biopsy can confirm the diagnosis of such disease. Common symptoms of mitochondrial encephalomyopathy such as stroke-like episodes, migraine, epilepsy, dementia, diabetes mellitus, and deafness can occur in isolation or in combination in individuals, all suggesting the possibility of mitochondrial disease. A clear family history also suggests the possibility of mitochondrial disease. If the patient’s clinical presentation, neurological examination and imaging features suggest mitochondrial encephalomyopathy, then DNA testing may be used for further screening. If the results of screening are not diagnostic, muscle biopsy is the best way to confirm the diagnosis. Cortical diffusion inhibition may be the mechanism by which headaches occur in patients with MELAS, but remains to be explored.