The overall goal of chronic hepatitis B treatment is to maximize the long-term suppression or elimination of the hepatitis B virus and to delay and halt disease progression. However, during long-term treatment with antiviral drugs, drug resistance has become a stumbling block on the way to achieving the overall goal of treatment for patients with chronic hepatitis B. Experts have developed three protocols to address drug resistance: prevention of drug resistance, prediction of drug resistance, and salvage therapy. Prevention of drug resistance: It refers to the selection of antiviral drugs with strong antiviral lowering ability and low incidence of drug resistance during the initial treatment of hepatitis B patients, proactively reducing the risk of drug resistance and minimizing the occurrence of drug resistance, which is essentially a preventive strategy. Predictive resistance: It refers to timely adjustment and change of the existing treatment strategy according to the patient’s response to early treatment after the patient is treated with an antiviral drug with a high incidence of resistance (i.e., with a low resistance genetic barrier) to delay or relatively reduce the risk of drug resistance, which is essentially a follow-up observation strategy. Salvage therapy: refers to changing the existing antiviral treatment regimen (adding or changing drugs) after the patient has developed drug resistance, which is essentially a remedial strategy. However, strategies to prevent drug resistance are difficult to apply in clinical practice. These difficulties arise mainly from the lack of patient understanding. This is because current guidelines for hepatitis B prevention and treatment in several countries and regions recommend that the most potent and least resistant antiviral drugs possible should be selected for initial hepatitis B treatment. However, these highly effective drugs also imply high prices. It is understood that among the four nucleoside analogues currently approved for chronic hepatitis B treatment in China, the five-year resistance incidence of lamivudine and adefovir is higher than 29%; the two-year resistance incidence of telbivudine for e antigen-positive patients and e antigen-negative patients is 21.6% and 8.6%, respectively; and the five-year resistance incidence of entecavir analogues, due to their ability to produce a high resistance genetic barrier in primary care patients, is The five-year incidence of drug resistance was 1.2%. However, entecavir is also 50% more expensive than other drugs. Therefore, if the doctor gives the patient entecavir at the beginning, the patient will often complain; why not give me a cheaper drug to try first, and then use it only if it doesn’t work. In this regard, the expensive drug in the eyes of patients; from the cost of a single tablet, the price is indeed higher than other drugs, but in the long run, the incidence of drug resistance in patients is reduced, but can save the cost of specialist visits, inpatient treatment, drug resistance testing, etc.. Therefore, if economic conditions permit, patients should choose a drug with strong viral suppressive effects at the time of initial treatment if possible.