Pyogenic granuloma is a benign vascular proliferation of the skin and mucous membranes, whose pathogenesis is not fully understood. Despite its benign nature, it can have a significant negative impact on patients’ quality of life, and therefore appropriate therapy is needed. Over the years, a lot of therapeutic modalities have been used in order to successfully treat this condition. This paper is an updated systematic overview of all the reported successful treatments described in the literature and was conducted according to the PRISMA guidelines for systematic reviews. Articles derived from the databases PubMed, EMBASE, and SCOPUS, published between 1981 and 2018, were analyzed for this study. In the literature, there are several studies, case series, and case reports that demonstrate encouraging results with the use of various methods, such as surgical intervention or laser treatment, but also with more conservative approaches, including the application of topical and systemic agents. The selection of the appropriate treatment should be made individually, depending on severity of the disease and patient characteristics. Both research efforts as well as clinical reporting are necessary in order to provide more insight on the management of these vascular tumors. This paper aims to provide a summarized update on the reported therapies and to raise awareness for the need to conduct larger systematic studies in order to adequately evaluate and compare the effectiveness of the presented therapeutic strategies.