Introduction: Beta-blockers are proven to be safe and cost-effective agents in treating multiple dermatological conditions, which is why they are considered as an interesting and good alternative therapeutic agent by dermatologists. To our knowledge, there has been no comprehensive systematic review to date summarizing the role of both systemic and topical betablockers in dermatology. Methods: In this systematic review, we aim to review recent and relevant published literature in order to provide a comprehensive evidencebased summary to inform dermatologists. Results: An electronic-based literature search was carried out during October-December 2021 in the databases PubMed (MEDLINE), SCOPUS (EMBASE), and Cochrane Library. Furthermore, bibliographic sources were also reviewed for the selected articles. We followed The Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA) guidelines. We reviewed published literature about the role of beta-blockers in dermatology for the time period (January 2016 to December 2021). Conclusions: A total of 126 publications were retrieved from different databases, of which 59 studies were finally included in our review after excluding non-eligible literature in accordance with our inclusion and exclusion criteria. The included articles consisted of meta-analyses, systematic reviews, clinical trials, retrospective and prospective cohort studies, case-control studies, case series, and case reports. In general, data in reviewed literature showed that both systemic and topical beta-blockers were reliable and safe therapeutic options in treating different dermatoses. Their effect has been studied as a mono-therapy, also as an adjuvant therapy combined with other current disease-specific therapeutic modalities such as lasers, radiation, chemotherapy, corticosteroids, or other betablockers options. Local and systemic adverse effects were mainly minor and non-significant.