The oxidation of organic substrates is of fundamental importance in nature and includes key transformations in organic synthesis and industry. Dioxygen (O₂) is potentially the greenest oxidant because O₂ is available in air and its reduction product is water, which is environmentally the most benign substance. However, the direct thermal oxidation of organic substrates with O₂ is spin-forbidden because the spin state of ground-state O₂ is triplet and the spin state of most organic substrates is singlet. Transition metal complexes can react with triplet O₂ in the presence of an electron source to produce metal–oxygen intermediates, such as metal-oxo and metal-hydroperoxo complexes, that can oxidize substrates under mild conditions. Various thermal and photocatalytic mechanisms of the oxidation of organic substrates by O₂ with transition metal complexes have been critically discussed by focusing on how metal–oxygen intermediates are produced in the presence of an electron source and then react with organic substrates. Metal–oxygen intermediates are more easily produced by the reactions of metal complexes with hydrogen peroxide (H₂O₂) and act as active catalysts for the oxidation of substrates by H₂O₂. The photocatalytic oxidation of water by O₂ to produce H₂O₂ has been combined with the catalytic oxidation of organic substrates by H₂O₂ to achieve the photocatalytic oxidation of organic substrates by O₂. The photocatalytic oxidation of organic substrates by O₂ with the use of water as an electron source has also been made possible by the use of inorganic and organic photocatalysts, which can be combined with transition metal complexes as catalysts for thermal reaction steps.