Hepatitis B virus (HBV) is an etiological agent of acute and chronic liver disease existing throughout the world. The high genetic variability of HBV is reflected by eight genotypes (A to H), each one with a particular geographical prevalence. The global pattern of HBV genotypes is associated with the distribution of human populations among the different continents and may reflect the patterns of human migrations. Genotypes F and H are considered indigenous to Latin America. The most prevalent genetic group of Central and South America, genotype F, is subdivided into two subtypes and five clusters associated with defined geographic areas. Genotype H has been described in Mexico and Central America. This pattern provides a tool to reconstruct the initial immigration of ancestral Amerindians from Asia and their further spread through Central and South America. Other HBV genotypes found in different Latin American countries may reflect migration from other geographical areas into the region. Genotypes A and D are the signature of the European colonization that started in the sixteenth century, including slave trade from Africa. Genotypes B and C indicate the arrival of people from Southeast Asia. The impact of HBV genotypes on the natural course of HBV infection and response to treatment has been studied recently and controversial results have been obtained. The majority of the current information concerns with genotypes B and C. In contrast, very few data are available on the Latin American HBV genotypes F and H. It has been reported that liver failure and death may be more frequent in patients infected with genotype F. More studies are needed to assess the association between H13V genotypes and clinical course of infection, especially in Latin America.