Background and Aims: Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Methods: The guideline was developed in compliance with the National Academy of Medicine standards. The guideline panel developed structured questions following the Population, Intervention Comparison, Outcomes (PICO) framework. The panel addressed 6 PICO questions covering prevention (maternal to infant transmission and horizontal transmission), surveillance for liver cancer (among hepatitis B surface antigen positive (HBsAg) persons co-infected with hepatitis C virus, hepatitis D virus and/or human immunodeficiency viruses and after HBsAg loss) and treatment (HBsAg positive persons in immune-tolerant or indeterminate phases as well as withdrawal of antiviral therapy), providing evidence-based recommendations on these topics. Four systematic reviews of the literature were conducted, and two existing systematic reviews were utilized to support the recommendations in this practice guideline. Conclusions: This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.