Molecular oxygen is the greenest of all possible oxidizing agents, but its specific electronic configuration eliminates the possibility of its direct reaction with organic substances. Single-electron transfer between triplet O2 and singlet organics is prohibited according to the Wigner spin selection rule. Moreover, attaching the first electron is disadvantageous even from a thermodynamic point of view. The authors will not consider the high-temperature processes, however, and will focus on the mechanisms for generating active oxygen species under normal temperature conditions. All methods of “soft” activation of oxygen can be conditionally divided into three main groups: photo-excitation; direct or sensitized initiation of a radical-chain oxidative process; and catalysis by transition metal ions with the inclusion of oxygen in the coordination sphere. New perspectives on molecular oxygen activation pathways and their application in some oxidative reactions including degradation of organic pollutants, organic synthesis, and environmentally significant reactions are discussed.