Since the launch of lamivudine for antiviral treatment of chronic hepatitis B in China in 1999, adefovir, entecavir and the latest tipifudine have been used in clinical practice. Over the past nine years, millions of patients with chronic hepatitis B have been relieved of their suffering and treated. However, because of the long duration of these drugs, the most frequently asked question in clinical work is: When can I stop taking them? To answer this question, first we need to clarify why the treatment time with nucleoside analogs is longer. Why does it take longer to treat with nucleoside analogs? First, the viral factor: because hepatitis B virus is a retrovirus, there is CCCDNA in hepatocytes, and nucleoside analogs are difficult to remove CCCDNA in these hepatocytes; and because HBV-DNA can integrate with host genes and escape the attack of nucleoside analogs; then there is the “new ” hepatocyte reinfection, constantly producing new hepatitis B virus. Second, the drug factor: the antiviral mechanism of nucleoside analogs is to directly inhibit viral replication, but not to completely kill the virus, so when the drug is used to play the antiviral effect, the virus is replicated again when not using the drug. Because of these two factors, the clearance of hepatitis B virus is a long-term process. So when can I stop taking the medication? For HBeAg-positive chronic hepatitis B, the accepted time to discontinue medication is when HBV-DNA reaches below detection level and HBeAg is converted. This means that the patient is treated with nucleoside analogues until the HBeAg turns negative and the HBeAb turns positive. When this HBeAg conversion is maintained for more than six months with continued treatment, discontinuation of the drug can be considered. For HbeAg-negative chronic hepatitis B, more long-term treatment is required until the patient’s HBsAg converts to negative before discontinuation can be considered. For patients with hepatitis B cirrhosis, they should take antiviral drugs for life and should not stop them easily. How can we meet the criteria for discontinuation as soon as possible? First of all, when deciding to give antiviral therapy to a patient, we have to choose the best time for treatment, that is, the patient is in the immune clearance phase, such as ALT2 ULN, or liver histology G2, when we can start the antiviral therapy. Secondly, in the selection of drugs, we should choose strong antiviral drugs. Among the nucleoside analogues currently used in clinical practice, the antiviral efficacy of entecavir and telbivudine is the strongest. The use of strong antiviral drugs can make hepatitis B virus replication is quickly inhibited, so that HBV-DNA quickly turn negative. The third is the problem of HBeAg conversion. Various nucleoside analogs, whether lamivudine or adefovir, entecavir, or telbivudine, may have HBeAg conversion during treatment, and the longer the drug is used the higher the rate of HBeAg conversion, however, the longer the drug is used the greater the likelihood of HBV mutation. HBeAg conversion rates are currently considered to be higher for telbivudine. Data show that the HBeAg conversion rate of telbivudine for HBeAg-positive chronic hepatitis B patients with baseline ALT ≥ 2×ULN at 104 weeks of treatment can reach 41.0%, and the HBeAg conversion rate is 36.0%. In conclusion, antiviral therapy with nucleoside analogs must be started during the patient’s immune clearance period; at the same time, choose a potent antiviral drug with a high HBeAg conversion rate, so that the discontinuation criteria can be achieved more quickly.