Acne vulgaris is a common dermatological condition characterized by hormonally-mediated sebum overproduction, follicular hyperkeratinization, and chronic inflammation of the pilosebaceous unit. Microbes, genetic susceptibilities, and various environmental factors have been linked to the pathogenesis of the condition. Over the last several years it has become apparent that patients with acne are under increased cutaneous and systemic oxidative stress. Moreover, the burden of oxidative stress may not be a mere consequence of acne; rather, the oxidative stress, lipid peroxidation in particular, may be an early event that helps to drive the acne process. Here, we explore the role of oxidative stress and review the preliminary research involving the administration of local and systemic antioxidants.