In 1988, it was reported that the full nucleotide sequences of 18 hepatitis B virus (HBV) strains clustered into four genetic groups (A to D) with more than 8% divergence between the groups. This classification of strains in terms of genome sequence has since proven to be an important tool in the understanding of HBV epidemiology and evolution and has been expanded to include three more genotypes. In parallel with the HBV genotypes described in humans, HBV strains isolated from different primates and hepadnaviruses found in woodchucks, ground squirrels, ducks and herons have been studied. Sequence differences between HBV genotypes can lead to structural differences at the level of the pregenome and can also lead to dramatic differences at the translational level when specific and commonly occurring mutations occur. There is increasing evidence that the clinical picture, the response to treatment and the long-term prognosis may differ depending on which genotype has infected the patient. The consideration of traditional serological patterns in a patient must therefore take the genotype of the infecting strain into account. Nucleotide variability between HBV strains has been used in several studies to trace routes of transmission and, since it is becoming increasingly clear that the differences between HBV genotypes are important, the need for reliable and easy methods of differentiating HBV genotypes has arisen. This review summarizes the knowledge of HBV genotypes with regard to their genetic, structural and clinically significant differences and their origin and evolution in the context of the hepadnaviruses in general.