Liquid-phase air oxidation of hydrocarbons, notably p-xylene, cumene, ethylbenzene/isobutane, cyclohexane, and n-butane, is of great scientific, technological, and commercial importance. This state-of-the-art paper covers the chemistry and engineering science aspects of these reactions. The role of uncatalyzed reactions and metal ion and mixed metal ion catalysts with bromide activation is discussed. An analysis is presented for the role of mass transfer in influencing the rate of reaction and selectivity for the desired product. Different types of reactors that are used, notably bubble-column reactors and mechanically agitated reactors, are analyzed, and a simple basis is provided for selection of reactors. Some emerging oxidation systems, notably oxidation of cycloalkenes (cyclohexene/cyclooctene/cyclododecene) and oxidation of isobutane under supercritical conditions, are presented. New strategies for conducting air oxidations, such as in biphasic systems (including fluorous biphasic systems), biocatalysis, photocatalysis, etc., are emerging and illustrate the considerable tailoring of the reaction microenvironment that is becoming possible. In some cases, it may be possible to manipulate chemo-, regio-, and enantioselectivity in these reactions.