The use of nitroxyl radicals, alone or in combination with transition metals, as catalysts in oxidation processes is reviewed from both a synthetic and a mechanistic viewpoint. Two extremes of reactivity can be distinguished: stable (persistent) dialkylnitroxyls, such as the archetypal TEMPO, and reactive diacylnitroxyls, derived from N-hydroxy imides, such as N-hydroxyphthalimide (NHPI). The different types of reactivity observed are rationalized by considering the bond dissociation energies (BDEs) of the respective N-hydroxy precursors, substrates and reaction intermediates. Reactive diacylnitroxyl radicals are generated in situ from the corresponding N-hydroxy compound. The protagonist, NHPI, catalyzes a wide variety of free radical autoxidations, improving both activities and selectivities by increasing the rate of chain propagation and/or decreasing the rate of chain termination. In the absence of metal co-catalysts improved conversions and selectivities are obtained in the autoxidation of hydrocarbons to the corresponding alkyl hydroperoxides. For example, cyclohexylbenzene afforded the 1-hydroperoxide in 97.6% selectivity at 32% conversion when the autoxidation was performed in the presence of 0.5 mol % NHPI, and the product hydroperoxide as initiator, at 100 °C. This forms the basis for a potential coproduct-free route from benzene to phenol. In combination with transition metal co-catalysts, notably cobalt, NHPI and related compounds, such as N-hydroxysaccharin NHS, afford effective catalytic systems for the effective autoxidation of hydrocarbons, e.g., toluenes to carboxylic acids, under mild conditions. In the case of the less reactive cycloalkanes, NHS proved to be a more active catalyst than NHPI which is attributed to the higher reactivity of the intermediate nitroxyl radical, resulting from the replacement of a carbonyl group in NHPI by the more strongly electron-attracting sulfonyl group. Stable dialkylnitroxyl radicals, exemplified by TEMPO, catalyze oxidations of, e.g., alcohols, with single oxygen donors such as hypochlorite and organic peracids. The reactions involve the intermediate formation of the corresponding oxoammonium cation as the active oxidant. Alternatively, in conjunction with transition metals, notably ruthenium and copper, they catalyze aerobic oxidations of alcohols. These reactions involve metal-centered dehydrogenations and the role of the TEMPO is to facilitate regeneration of the catalyst (Ru and Cu) and oxidation of the alcohol (Cu) via hydrogen abstraction or one-electron oxidation processes. Detailed mechanistic investigations, including kinetic isotope effects, revealed that oxoammonium cations are not involved as intermediates in these reactions. In contrast, oxoammonium cations are involved in the aerobic oxidation of alcohols catalyzed by the copper-dependent oxidase, laccase, in combination with TEMPO. This different mechanistic pathway is attributed to the much higher redox potential of the copper(II) in the enzyme. Similarly, N-hydroxy compounds such as NHPI also act as mediators in laccase-catalyzed oxidations of alcohols. These reactions are assumed to involve one electron oxidation of the N-hydroxy compound, leading to the formation of a proton and the nitroxyl radical, which abstracts a hydrogen atom from the substrate. However, neither of these laccase-based systems has, as yet, attained the activity and scope of the TEMPO/hypochlorite system.