The association between immunosuppressive therapy for dermatologic conditions and the subsequent reactivation of hepatitis B is of major medical concern. It remains a point of interest across multiple disciplines, including hepatology, dermatology, rheumatology, and infectious disease. Accordingly, we present an evidence-based practice algorithm on how best to approach a patient with presumptively cleared hepatitis B infection when anticipating the initiation of immunosuppressive therapy. This guide delineates the risk of reactivation by taking into account the immunosuppressive agent of choice and presents recommendations for antiviral prophylaxis and laboratory monitoring. Booster vaccination as a potential to decrease the risk of hepatitis B reactivation is likewise discussed. (SKINmed. 2021;19:-0).