HBV reactivation is commonly seen during immunosuppressive therapy and is associated with high incidence and mortality rates due to hepatitis outbreak and liver decompensation, and therefore, it should be taken seriously. However, the prevention and management of this potential complication is still a difficulty in clinical practice. This article reviews the diagnostic criteria and clinical outcomes of HBV reactivation, discusses the association of immunosuppressive therapy with the risk of HBV reactivation, and outlines the strategies for the prevention of HBV reactivation and recent advances. It is pointed out that early identification of patients with HBV infection before immunosuppressive therapy is of vital importance, and the initiation of antiviral therapy at the right moment based on risk stratification can effectively reduce the risk of HBV reactivation. We hope that this review can increase the awareness of HBV reactivation among clinicians and provide an effective reference for optimizing the management and prevention of HBV infection.