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Acute dermatitis is the most common radio-induced side effect during treatment for head and neck cancer. The use of a wide variety of agents is reported to handle skin toxicity. Our aim was to review the literature and synthesize current available evidence. A comprehensive search was performed on multiple electronic databases until February 2017 and a systematic approach was carried out according to PRISMA guidelines. A total of 17 papers (950 patients on the whole) met the inclusion/exclusion criteria, with 12 randomized controlled trials and five nonrandomized observational and prospective studies. Generally speaking, there was no strong evidence to support the superiority of any specific intervention neither in prevention nor in therapeutic settings. Well-designed randomized studies including quality of life measurements are needed.