Exercise is a promising therapeutical option for the treatment of mitochondrial myopathies. Its efficacy and safety have been proven in various studies. In patients with mitochondrial myopathy, resistance training and aerobic exercise training lead to widely diversified effects: resistance training is thought to normalize the mitochondrial DNA (mtDNA) genotype in mature myofibers by enhancing the incorporation of satellite cells and thereby increasing the ratio of wild-type to mutant mtDNA (“gene shifting”). Aerobic exercise training induces mitochondrial biogenesis and helps breaking the vicious circle of low oxidative phosphorylation capacity, exercise intolerance, and progressive muscular deconditioning. Certain drugs act as inductors of mitochondrial biogenesis but their safety and efficacy in patients with mitochondrial myopathy have to be further investigated.