Chronic hepatitis B is a long-term progressive disease caused by the continuous replication of the hepatitis B virus. Therefore, as long as there are indications for antiviral therapy, patients should receive standardized antiviral therapy, with the aim of delaying or curing the disease and reducing the occurrence of cirrhosis and primary liver cancer through effective antiviral therapy. However, before initiating antiviral therapy, one should understand the characteristics, efficacy, course of treatment and precautions of different drugs, so as to select more appropriate treatment drugs and programs according to the different conditions of patients. The two main classes of antiviral drugs are nucleoside (acid) analogs and interferons. Nucleoside (acid) analogs directly inhibit viral replication by acting on the reverse transcriptase active site of HBV polymerase. For patients in the decompensated stage of cirrhosis, both domestic and international guidelines recommend potent nucleoside (acid) analogs with low drug resistance as first-line therapy; however, for patients in the compensated stage of liver disease, although both drugs are available, in addition to the need for rapid and potent viral inhibition, consideration should be given to whether drug resistance is likely to occur, whether HBeAg serological conversion and/or HBsAg clearance and durable immune response after drug discontinuation can be achieved, and drug safety. The drug safety is also a factor. According to China’s 2010 edition of the Guidelines for the Prevention and Treatment of Chronic Hepatitis B, HBeAg-positive patients with chronic hepatitis B who have undergone HBeAg seroconversion with nucleoside (acid) analog therapy should continue to consolidate treatment for at least 1 year and maintain each response in two consecutive examinations (each at least 6 months apart) for a total duration of more than 2 years before considering discontinuation of the drug. In fact, less than 30% of patients can meet this discontinuation criterion, and the percentage of those who can maintain the response after discontinuation is even lower. Clearly, for the majority of patients treated with nucleoside (acid) analogs, they are choosing a path of treatment that requires long-term adherence. In contrast, long-acting interferons, which combine both antiviral and immunomodulatory mechanisms of action, have an advantage in achieving HBeAg serologic conversion and HBsAg clearance for immune control and clinical cure. 2012 EASL guidelines clearly state that the best chance of achieving HBeAg serologic conversion in HBeAg-positive hepatitis B patients is with pegylated interferon alpha-2a therapy. Results from clinical studies confirm that the HBeAg serologic conversion rate at 24 weeks after discontinuation in HBeAg-positive patients treated with pegylated interferon alfa-2a for 48 weeks is approximately 1 in 3, while for patients with high ALT and low HBV DNA at baseline this rate exceeds 60%, much higher than the data for nucleoside (acid) analogs. Therefore, the choice of long-acting interferon therapy can help patients who expect to pursue higher treatment goals with a limited course of therapy, especially those who are expected to have a higher chance of response with interferon therapy, to have a chance of being on the path to a cure. In addition, it is encouraging to note that the results of recent studies on quantitative hepatitis B surface antigen (HBsAg) testing have pushed the efficacy of interferon therapy to a new level. Some studies have shown that quantitative HBsAg levels are more accurate than HBV DNA in predicting the efficacy of interferon. The faster and greater the decrease in HBsAg levels during interferon treatment, the better the treatment effect. Determining the course and regimen of interferon based on the dynamic changes in HBsAg levels during treatment can further improve the efficacy and increase the success rate of treatment. Finally, we would like to remind patients that whether they are treated with interferon or nucleoside (acid) analogs, antiviral treatment is a process that needs to be managed scientifically and must be done through regular channels, such as regular hospitals and regular pharmacies, under the guidance of experienced doctors to choose a more suitable regimen and pursue better treatment results.