First, chronic hepatitis B is an infectious rather than a genetic disease, and therefore theoretically does not require lifelong treatment. Second, clinical studies have shown that short courses of nucleoside analogue therapy are effective in patients who are refractory or have severe clinical manifestations. In such cases, nucleoside analogs can be safely discontinued when clinical and virological responses occur. Alternatively, nucleoside analogs can be discontinued prophylactically in patients receiving immunosuppressive therapy, 6 weeks to 6 months after the patient has completed immunosuppressive therapy. Third, even for patients with chronic hepatitis B, nucleoside analogs can be discontinued once clinical evidence of HBV DNA negativity has persisted for a certain period of time as well as attainment of HBeAg seroconversion, and after another 6 months of consolidation therapy. The rate of HBeAg seroconversion and its persistence depend on host factors (e.g., patient age, gender, HBV infection route, immune status, and liver disease activity) and virologic factors (genotype, HBeAg status, and genetic mutations). Clinicians should have a clear understanding of the above factors. In young, HBeAg-positive, genotype A or B patients with active liver disease (high ALT or histology showing active necroinflammation) and no cirrhosis, the rate of HBeAg conversion after treatment is high and nucleoside analogs can be discontinued after 6 months of consolidation therapy, whereas in older, HBeAg-negative, genotype C, with low liver disease activity or cirrhosis, it is recommended to give long-term nucleoside analogue therapy, but even in these populations, nucleoside analogs can be discontinued in certain patients. Many diseases require long-term treatment such as hyperlipidemia, hypertension, and diabetes mellitus. Although long-term nucleoside analogs are costly and have patient compliance issues, the overall benefits outweigh the harms. It is now accepted that consolidation of therapy for at least 1 year after HBeAg disappearance or seroconversion is required to ensure a durable response after discontinuation of the drug. However, there is a lack of long-term data to support that patients do achieve durable responses, and HBV DNA is still detectable in many patients. HBeAg-negative patients are prone to relapse once they stop treatment, even though HBV DNA may remain negative for several years. Of course, a small percentage of patients will experience the disappearance of HBsAg, and the duration of HBV DNA reversion will last longer. If a patient develops cirrhosis or is at high risk for liver cancer, then long-term treatment is necessary.