In this Forum Article, we discuss the use of dioxygen (O-2) in oxidations catalyzed by polyoxometalates. One- and two-electron-transfer oxidation of organic substrates is catalyzed by H5PV2Mo10O40 and often occurs via an outer-sphere mechanism. The reduced polyoxometalate is reoxidized in a separate step by O-2 with the formation of water. H5PV2Mo10O40 also catalyzes electron transfer-oxygen transfer reactions. Here, in contrast to the paradigm that high-valent oxo species are often stronger oxygen-transfer species than lower-valent species, the opposite occurs. Thus, oxygen transfer from the catalyst is preceded by electron transfer from the organic substrate. The monooxygenase-type reduction of O-2 with polyoxometalates is also discussed based on the formation of a stable iron(III) hydroperoxide compound that may have implications for the oxidation of other lower-valent polyoxometalates such as vanadium(IV)-and ruthenium(II)-substituted polyoxometalates. Finally, the formation of hybrid compounds through the attachment of electron-accepting polyoxometalates to coordination compounds can modify the reactivity of the latter by making higher-valent oxidation states more accessible.