Genetic and linguistic data suggest that the Na-Dene, of which the Athabaskans are the largest group, are part of a later immigration into the Americas than the first Amerind immigration. Whether a second and third immigration can be separated seems unlikely but continued cross-Bering Strait exchanges may have masked what was a greater separation in the past. The movement of tribes into Siberia appears to have involved a genetic bottleneck leading to at least one disease allele shared by Eskimo/Aleuts and Navajos and a second possibly shared by the Navajo and a Siberian population, but not the same Siberian population that share deep linguistic affinities with the Navajo. A second bottleneck appears to have occurred with the migration of Athabaskans from Northwest North America to the Southwestern United States along the Rocky Mountains. This bottleneck is reflected in several rare recessive diseases shared by the Navajo and Apache. Finally, the Navajo were captured and imprisoned under conditions which led to severe population loss. This, and the “hiding away” of a small number of Navajos in what is now the Western portion of the reservation, led to a Navajo-specific bottleneck(s) resulting in an increased frequency of several rare recessive diseases among the Navajo. Prejudice against human genetic research is high among the Southwestern Athabaskans but attempts to bridge the gap are now occurring. The involvement of Navajo scientists in this process is especially encouraging. © 2009 Wiley-Liss, Inc.