High-valent iron(IV)–oxo species have been implicated as the key reactive intermediates in the catalytic cycles of dioxygen activation by heme and non-heme iron enzymes. Our understanding of the enzymatic reactions has improved greatly via investigation of spectroscopic and chemical properties of heme and non-heme iron(IV)–oxo complexes. In this Account, reactivities of synthetic iron(IV)–oxo porphyrin π-cation radicals and mononuclear non-heme iron(IV)–oxo complexes in oxygenation reactions have been discussed as chemical models of cytochrome P450 and non-heme iron enzymes. These results demonstrate how mechanistic developments in biomimetic research can help our understanding of dioxygen activation and oxygen atom transfer reactions in nature.