Approximately 2 billion people worldwide are infected with HBV, and 350 million people are chronic carriers. HBV is classified into nine genotypes (A to I). Genotype F is the most prevalent in the Spanish-speaking countries and in the Amerindian population in South America. HBV genotype F was primarily found in indigenous populations from South America and is divided into four subgenotypes (F1 to F4). Subgenotype F1 is further divided into F1a (found in Costa Rica and El Salvador) and F1b (found in in Alaska, Argentina and Chile). Subgenotypes F2 and F3 cocirculate in the north of South America: F2a is found in Brazil and Venezuela, F2b is described only in Venezuela, F3 is frequent in Colombia, Venezuela and Panama, and F4 is reported from the central and south areas of South America, including Bolivia, Argentina and southern Brazil. HBV genotypes and subgenotypes have distinct geographical distributions. It is currently under discussion whether they are associated with different prognoses, considering the patterns of severity of liver diseases in various populations. Furthermore, global human migrations affect the pattern of genotype distribution, introducing genotypes differing from those found in the original inhabitants.