The mitochondrial respiratory chain is the final step in oxidative metabolism and plays an essential part in the mechanisms of energy production. It is composed of five enzymatic complexes under the dual control of nuclear and mitochondrial genomes. The disorders caused by respiratory chain defects are heterogeneous, mainly affecting organs and tissues which are functionally dependent on oxidative metabolism, such as brain, muscle, myocardium, kidney and liver. The activity of the enzymatic complexes may be measured in any tissue or organ, but skeletal muscle is usually used since it is post-mitotic and permits correlation with morphological studies. Defects in the electron transport chain may affect one or more complexes. Monoenzymopathies are characteristic of nuclear alterations, particularly if there is phenotype histo-specificity. However, mutations of the structural genes of the mitochondrial DNA (mtDNA) may also produce specific defects. Combined defects are characteristic of mtDNA alterations due to reduced synthesis of mitochondrial proteins.