HBV reactivation (HBVr) can occur due to the ability of HBV to remain latent in the liver as covalently closed circular DNA and by the capacity of HBV to alter the immune system of the infected individuals. HBVr can occur in patients undergoing hematopoietic stem cell transplantation (HSCT) with a clinical spectrum that ranges from asymptomatic infection to fulminant hepatic failure. The risk of HBVr is determined by a complex interplay between host immunity, virus factors, and immunosuppression related to HSCT. All individuals who undergo HSCT should be screened for HBV. HSCT patients positive for HBsAg and also those HBcAb-positive/HBsAg-negative are at high risk of HBV reactivation (HBVr) due to profound and prolonged immunosuppression. Antiviral prophylaxis prevents HBVr, decreases HBVr-related morbidity and mortality in patients with chronic or previous HBV. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naïve recipients and their donors against HBV prior to HSCT has an important role in the prevention of acquired HBV infection. This narrative review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of HBVr in HSCT.