Slow hepatitis B is an “ancient” disease, although hepatitis epidemics have been recorded in 2000 B.C., but the diagnosis and treatment of slow hepatitis B did not develop quickly until after World War II, when Western physicians clarified that the disease was caused by blood transmission and called it hepatitis B. In 1963, physicians found surface antigens for the first time in the blood of Australian natives, which gradually became the criterion for diagnosing hepatitis B. In the past, hepatitis B has become the most serious disease in the world. In 1963, doctors found surface antigen in the blood of Australian natives for the first time, and it was gradually used as a criterion for diagnosing hepatitis B. Since then, although medical practitioners have continued to fight against hepatitis B, however, even thirty years ago, there was still no effective treatment for slow hepatitis B. Rest and liver protection were the most mentioned, which shows the helplessness of the doctors in treating slow hepatitis B. At the end of the twentieth century, with the accumulation of experience in interferon therapy and the successive marketing of nucleoside (acid) analogs, the treatment of slow hepatitis B was only gradually established, and the 2000 version of China’s guidelines proposed for the first time that chronic hepatitis should emphasize antiviral therapy. Today, antiviral therapy has become the core treatment program for chronic hepatitis B due to its clear efficacy confirmed by a large number of studies and clinical practice. Finally, there are effective drugs for the treatment of chronic hepatitis B. However, a new question arises. Patients with chronic hepatitis B often ask their doctors before starting antiviral treatment: which drug is the best antiviral treatment for chronic hepatitis B? There are two major classes of antiviral drugs for hepatitis B. Currently, long-acting interferon and nucleoside (acid) analogs are commonly used. These two types of drugs have different mechanisms of action, and the characteristics of efficacy are also somewhat different, rather than choosing which treatment is good, it is better to say that each is suitable for what kind of conditions and needs. First, let’s talk about nucleoside (acid) analogs, these drugs can inhibit the replication of the hepatitis B virus, and its efficacy is characterized by a faster reduction in the serum level of the hepatitis B virus, which can bring about the alleviation of the disease. However, this type of drug requires long-term treatment, because once the drug is discontinued, the inhibitory effect of the drug on the replication of the hepatitis B virus will disappear, and the serum level of the hepatitis B virus of most patients will rise again, and the disease will recur. Of course, if patients can adhere to the medication for a long period of time, they can also maintain the stability of the disease for a long time, which is also a very good treatment effect. If one is willing to take long-term treatment, this type of drug is a suitable choice, but it is better to choose a strong and low-resistance drug to reduce the risk of drug resistance after long-term treatment. Another type of antiviral drug, long-acting interferon, is characterized by its ability to achieve a high percentage of e-antigen conversion and surface antigen clearance through a fixed course of treatment, and to achieve a durable response after discontinuation of the drug. This is the best result that can be achieved with current antiviral therapy. Authoritative guidelines recommend that patients with chronic hepatitis B who want to stop medication, rather than long-term treatment, consider trying long-acting interferon therapy first. Some experts refer to this as a “once-in-a-lifetime” approach, meaning that patients with chronic hepatitis B should try long-acting interferon therapy at least once in their treatment to pursue the opportunity to stop. According to the results of the current study, the efficacy of long-acting interferon therapy is better if patients with lower virologic levels and higher transaminase levels receive long-acting interferon therapy prior to the initiation of antiviral therapy. In conclusion, the treatment of chronic hepatitis B should be based on antiviral therapy, and the specific choice of medication to be made is based on the condition and the willingness to treat. And, no matter which treatment you choose, follow the doctor’s prescription to get good results.