Drug resistance is an extremely important issue in the treatment of chronic hepatitis B with nucleoside (acid) analogs, and patients will always face drug resistance problems during long-term or even lifelong nucleoside (acid) analog therapy. Learning and understanding some relevant knowledge can help to enhance communication with doctors in order to prevent or detect and manage drug resistance problems early. Doctors often use highly generalized terminology to describe complex medical issues, and knowing these terms can help patients better understand their condition and make it easier to “keep up” with them during medical appointments or when attending medical education. Terms related to the manifestation of drug resistance: The earliest manifestation of drug resistance is an abnormal virological level, which doctors refer to as a virological breakthrough, followed by a biochemical breakthrough in more than 90% of patients. Virologic breakthrough: Patients who achieve a partial or complete virologic response without a change in therapy have a 1lgIU/ml increase in HBV DNA levels from the lowest point in therapy, confirmed by 2 tests more than 1 month apart. Biochemical breakthrough: ALT rises above the ULN in patients with pretreatment ALT ≥ 2 ≥ the upper limit of normal (ULN),and whose ALT has fallen to normal during treatment, in the absence of a change in treatment. Terms related to drug resistance testing: In addition to looking at clinical manifestations, resistance genetic testing is a laboratory test to clarify whether drug resistance has occurred. Gene resistance: Mutations in loci associated with hepatitis B virus resistance are detected during the course of antiviral therapy. With the results of this test, it is possible to clarify not only whether drug resistance has occurred, but also what nucleoside (acid) analogs the patient is resistant to. Terminology related to the type of resistance: Once resistance has occurred it may be to a single nucleoside (acid) analogue, but it may also be to multiple nucleoside (acid) analogues, the latter being called multidrug resistance. Multidrug resistance is a more serious situation and is often ineffective even when add-on strategies are used. In addition, there is a situation where cross-resistance causes patients to be less sensitive to other nucleoside (acid) analogs and susceptible to drug resistance. Multidrug resistance: resistance to at least 2 NAs that do not have a cross-resistance profile and are of different classes. Cross-resistance: Resistance variants that occur against 1 antiviral drug, resulting in reduced susceptibility of the virus to another nucleoside (acid) analogue or analogues, or even initial resistance. For example, lamivudine and entecavir have cross-resistance problems, and patients resistant to lamivudine who took entecavir for 5 years had a resistance incidence of 51%. In conclusion, drug resistance is the difficulty of nucleoside (acid) analogs for the treatment of slow hepatitis B. Patients should take a responsible attitude towards themselves, acquire more knowledge, communicate well with their doctors, and cooperate with them for scientific prevention and treatment.