Hepatitis B virus (HBV) infection is a serious global public health issue. At present, clinical cure is the ideal endpoint for hepatitis B treatment. That is to say, after the completion of treatment, the serum hepatitis B virus surface antigen (HBsAg) is negative, with or without the presence of antibody against hepatitis B virus surface antigen (anti-HBs), undetectable HBV DNA, liver biochemical indicators within normal range, and improved liver tissue lesions. However, it is difficult to achieve a satisfactory clinical cure effect based on the existing therapeutic drugs. To this end, scientists have conducted many explorations, whether it is a combination of nucleos(t)ide analogues and pegylated interferon therapy strategies, or timely termination of antiviral drug treatment, or accelerate the research and development of innovative drugs. The road to clinical cure of hepatitis B is obstructive and long, with full of opportunities and controversies, but the lead is about to come. We always believe that through unremitting efforts, the dream of helping chronic hepatitis B patients to obtain clinical cure or even complete cure will eventually come true.