Optimizing treatment should be about getting greater treatment benefits for less treatment cost. Treatment is also called management and is not the same as medication. Receiving regular follow-up and not using any medication are also part of treatment. The eradication of chronic hepatitis B will remain an ideal rather than a reality for quite some time to come, although clinical cures have been achieved in individual patients. Patients with chronic hepatitis B require long-term management by a physician. Optimization of the treatment of chronic hepatitis B includes at least three components: patient preference, protocol preference, and regimen preference. The optimization of the three components is a dynamic rather than a static process. How is therapeutic drug optimization performed? According to current research, no more reliable predictors, programs or models have been found. Experience and rational judgment based on senior physicians with clinical research capabilities still prevail. The disappearance of hepatitis B surface antigen is usually considered a criterion for clinical cure, and long-term follow-up of patients with disappeared hepatitis B surface antigen has shown that liver disease no longer progresses and tends to recover. Naturally occurring hepatitis B E antigen disappearance usually predicts that liver disease will not progress and will tend to recover within a limited period of time, and also predicts an increased chance of future hepatitis B surface antigen disappearance. However, naturally occurring is not the same as drug-associated hepatitis B E antigen disappearance. Drug-associated hepatitis B E antigen disappearance or similar to naturally occurring hepatitis B E antigen disappearance, but also includes drug-induced temporary effective immune response resulting in or direct viral suppression resulting in reduced hepatitis B E antigen expression. Naturally occurring hepatitis B E antigen disappearance is associated with at least the sex and age of the organism, the level of hepatitis B surface antigen expression and differences in the regulation of different antigen expression by the hepatitis B virus, and ultimately with a shift in the pattern of the immune response to control the virus in a more efficient direction. Drug-related disappearance of hepatitis B E antigen is not necessarily accompanied by a shift in the mode of immune response to control the virus in a more efficient direction. Only a concomitant shift in the immune response pattern to a more effective control of the virus can lead to the non-progression and recovery of liver disease within a limited time frame. In other words, only those patients whose immune response pattern has changed to a more effective direction in controlling the virus will stop progression and tend to recover within a limited period of time after discontinuation of the drug. It should be clearly noted that, according to current studies, no reliable predictor, program or model has been found to predict that drug-related disappearance of hepatitis B E antigen is part of a shift towards a more effective mode of immune response to control the virus. Therefore, patients with chronic hepatitis B, with or without drug therapy, still need to be managed and monitored by their physicians on a long-term basis. Understood from a practical perspective, optimal treatment of chronic hepatitis B is synonymous with individualized treatment, but with a greater emphasis on the cost-benefit ratio.