The electron transport chain is the final stage of aerobic respiration. NADH or succinate from glycolysis, fatty acid oxidation, or tricarboxylic acid cycle passes its electrons to the electron transport chain on the inner mitochondrial membrane. As the electrons are passed on along the electron transport chain, the electrons’ energy potential is used to pump protons into the space between the inner and outer mitochondrial membranes. The electrochemical gradient resulting from these pumped protons is used to fuel ATP synthesis. Regulation of the electron transport chain plays a role in energy metabolism-related diseases such as obesity, insulin resistance, hepatic steatosis, and diabetes mellitus. Dysfunction of electron transport chain regulation contributes to neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease, too. The mitochondrial electron transport chain is the source of leaked electrons creating reactive oxygen species and contributing to aging. In this review, we will discuss current knowledge about the respiratory supercomplexes of the electron transport chain and the issues in disputes.