Mitochondria contain respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce a main part of cellular energy in the form of ATP. Mitochondrial disorders occur either due to sporadic or inherited mutations of the genes located in the nuclear or mitochondrial DNA or due to other exogenous factors. Although several proteins related with signalling, assembling, transporting, and enzymatic functions can be impaired in mitochondrial disorders, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial disorders usually show a chronic and slowly progressive course and present with multiorgan involvement with varying onsets between birth and late adulthood. They represent a diagnostic challenge because of their wide variations in the presentation and the course. The systems frequently affected in mitochondrial disorders are the peripheral nervous system, brain, endocrine system, heart, eyes, ears, guts, kidneys and bone marrow. Although there is actually no specific therapy and cure for mitochondrial disorders, the rapidly increasing understanding of the pathophysiological background of mitochondrial disorders may further facilitate the diagnostic approach and open perspectives to the future and possibly causative therapies.