Chronic hepatitis B (CHB) is a global public health problem and is the leading cause of cirrhosis and liver cancer worldwide. Despite significant morbidity and mortality of CHB, there remains lack of knowledge and awareness in screening patients at risk. HBV reactivation is well documented in patients previously exposed to HBV receiving immunosuppressive agents and is characterized by a rise in serum HBV DNA with ALT elevation. The delayed recognition of reactivation can lead to significant clinical consequences, including liver failure and death, and can be prevented with antiviral treatment. The challenges surrounding the management of HBV reactivation include a lack of awareness of this phenomenon, heterogeneity in clinical practice for CHB, and a paucity of data to guide clinicians in the prevention and treatment of reactivation. Collaboration and partnership across medical specialties will be essential in the development of consensus guidelines.