Nucleoside (acid) analogs are important drugs for the treatment of slow hepatitis B. They are also widely used anti-hepatitis B virus drugs. These drugs have a relatively good anti-hepatitis B virus effect and can inhibit hepatitis B virus replication, as shown by the ability to quickly reduce or turn negative the level of hepatitis B virus in the blood, and stabilize the disease through long-term maintenance treatment. However, some patients treated with nucleoside (acid) analogs do not achieve such efficacy, a condition known medically as poor response or partial virologic response, specifically in patients who are well adhered to nucleoside (acid) analog therapy and who adhere to the medication, the hepatitis B virus decreases by more than 2log10IU/ml from baseline (i.e., at the start of therapy) at 24 weeks of treatment, but is still detectable. It should be noted that although poor response has excluded adherence problems in the medical definition, however, the so-called poor efficacy and poor response in clinical practice are often related to the patients’ medication taking habits, and missed doses or unauthorized discontinuation are a major cause of efficacy loss. Therefore, when poor efficacy is detected, it is important to first review whether there are problems in this area and try to improve it to safeguard the efficacy. If the efficacy is poor, but there is no problem with dosing, it is a true poor response. Nucleoside (acid) analogs are currently available in five drugs, and these five drugs can be divided into two categories: entecavir and tenofovir, which have a strong high resistance genetic barrier, and lamivudine, adefovir and tipifudine, which have a low potency and low resistance genetic barrier. The former have a higher rate of virologic response, while the latter show a relatively higher incidence of poor response. Therefore, both national and international guidelines recommend treatment with entecavir or tenofovir as a priority at the time of initial treatment, and switching to tenofovir or adding adefovir for patients already started on lamivudine, tenbivudine or adefovir if the viral quantification is >300 copies/ml after 24 weeks of treatment. However, there are no consistent treatment recommendations on whether treatment regimens need to be adjusted for poor responders to entecavir or tenofovir. However, there are some findings that suggest that adding or switching to long-acting interferon therapy for poor responders to nucleoside (acid) analogs can also improve outcomes, a treatment option that some experts have called a “silver lining” and is attracting increasing attention.