The oxo‐functionalization of organic substrates with the aid of metal oxo moieties is of fundamental importance not only in nature but also in academic and industrial research. Nevertheless the corresponding reaction mechanisms remain among the most enigmatic in chemistry and few of them are understood in detail. Recent research efforts have resulted in significantly improved information: In the cases of many oxygenation reactions evidence has been provided for the occurrence radical intermediates, even though the high selectivity observed suggests to a different mechanism. Examples stem from various areas of chemistry and include processes involving molecular metal oxo complexes, gas‐phase and matrix‐isolated species, metalloenzymes, and solid‐state oxide surfaces. This Review treats this seemingly wide variety of systems with the aim of providing an overview of common reactivity patterns and principles, as well as open problems.