Poor response to hepatitis B antiviral therapy is a difficult problem, and poor early response is associated with high rates of distant drug resistance. Single-drug sequential therapy has been tried in the past, but it is now uniformly believed that single-drug sequential therapy can lead to multiple drug resistance, which hinders the achievement of chronic hepatitis B treatment goals. Currently, we advocate the use of potent, low resistance drugs for people with high viral load and cirrhosis, or the early use of nucleoside (acid) drug combinations without cross-resistance sites. Combination therapy can improve the efficacy, prevent drug resistance and resist drug resistance.