Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting more than 20% of children and 7% of adults in the world, with a wide variation worldwide. The prevalence of AD is increasing, probably due to the higher levels of pollution. Among the symptoms of AD (eczematous skin lesions with lichenification and excoriation, dry skin and a susceptibility to skin infections), pruritus is probably the major concern for the patients, as it can impact negatively their quality of life. Pathogenesis of AD, although not completely elucidated, comprises a combination of genetic, environmental and immunological factors. Involvement of oxidative stress, defined as the formation of oxidants in the cells of the human body acutely or chronically exceeding the antioxidant defence capacities, in the pathogenesis of AD has long been suggested and is now widely accepted. Superoxide dismutase (SOD) is a potent enzymatic antioxidant found in most living organisms. Besides its antioxidant properties, SOD is also displaying an anti-inflammatory and immunomodulating activity. Various clinical studies are reporting the use of topical SOD in AD, and concluded with its efficacy and tolerability in this indication. Interestingly, SOD has a potent antipruritic activity which is useful in the treatment of AD. In spite of its high molecular weight, the skin absorption of SOD was demonstrated, probably through the skin appendages.