The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.