A review was made in relation to the molecular variability present in North, Central, and South American Indian populations. It involved results from ancient DNA, mitochondrial DNA in extant populations, HLA and other autosomal markers, X and Y chromosome variation, as well as data from parasitic viruses which could show coevolutionary changes. The questions considered were their origin, ways in which the early colonization of the continent took place, types and levels of the variability which developed, peculiarities of the Amerindian evolutionary processes, and eventual genetic heterogeneity which evolved in different geographical areas. Although much information is already available, it is highly heterogeneous in relation to populations and types of genetic systems investigated. Unfortunately, the present trend of favoring essentially applied research suggest that the situation will not basically improve in the future.