Background: Hepatitis B virus (HBV) infection is a global public health burden, affecting nearly 300 million people around the world. Due to HBV population is considered to be represented as a viral quasispecies with genetic diversity, some reports showed that different genotypes of HBV have different viral effects, though the emergence of antiviral drugs that effectively inhibit viral replication, however, HBV infection has still not been eradicated and further research is needed. Summary: HBV has been classified into at least ten genotypes (A-J) and more than 40 subgenotypes based on an intergroup or intragroup nucleotide difference across the whole genome, respectively. Inter genotypic recombinants were also observed during the HBV evolution. HBV genotypes and subgenotypes have distinct ethno-geographical distributions, as well as evident differences in their biological characteristics. HBV genotypes and subgenotypes also have close association with disease severity, long-term clinical outcomes, and response to antiviral therapy. KeyMessages: In this review, we up-dated the epidemiological characteristics, clinical features and prognosis of HBV infection with dissimilar genotype/subgenotypes, to better understanding and developing individualized prevention and treatment strategies.