1. The original homeland of the first Amerindians remains elusive, different results having been obtained using mtDNA, autosomal, sex-chromosome, or viral parasitic information; 2. Different waves of migration had been postulated on the basis of mtDNA, Y chromosome, and other types of genetic and non-genetic (for instance, linguistic) evidences. The suggested dates of their occurrence are also variable; 3. The level of genetic variability of Amerindians, as compared to other groups, cannot be easily ascertained. There is restriction of variability for some of the mtDNA and HLA markers, but this is not necessarily so for other genetic traits. On the other hand, interpopulation variation seems to be more marked in Amerindians than elsewhere, probably due to their population structure; 4. The most exciting differences between Amerindians and non-Amerindians are those related to the HLA system, with the indication of allele turnover and antigen-driven positive selection especially at the B locus, probably due to historical processes of population changes in number, and to diversified exposure to infectious agents; 5. Certainly, many genetic differences could be detected along the continent. Some of them are clinal, while others are more abrupt. In a way this would be expected, due to the varied amount of population movements and of distinct environments they had to face.