This article summarizes research conducted on the genetic structure of circumpolar populations of Alaska, Siberia, and the Aleutian Archipelago from 1977 to present. Three research programs are described: (1) 1977–1978, on the genetics of small, Yupik-speaking communities of St. Lawrence Island (Savoonga and Gambell) compared with Inupk communities of King Island and Wales, Alaska. This research, based on 25 standard protein and blood markers, demonstrated genetic discontinuity between the populations of the two language groups, patterns of gene flow, and the co-evolution of genes and languages in the Arctic. (2) 1989–1995, on the origins of Native American populations in Siberia. DNA was collected from two Evenki reindeer herding populations: Surinda and Poligus, a Ket community on the Stony Tunguska River, Sulamai, and a cattle-herding village from Gorno Altai, Mendur-Sokhon. Using an assortment of molecular markers, such as mitochondrial DNA, DNA fingerprints, and nonrecombining Y-chromosome markers, this research demonstrated the close genetic affinities among the Siberian and the Native American indigenous groups. (3) 1999 to present, on the origins of populations of the Aleutian Islands and their underlying genetic structure. A total of 11 inhabited islands from the Aleutian Archipelago were sampled and based on mtDNA sequences was shown to cluster tightly with Siberian Eskimo and Chukchi populations. Evidence of genetic drift through founder effect was demonstrated on Bering Island, where the D2 haplotype was fixed. Genetic discontinuity based on mtDNA was shown through SAMOVA between Kamchatkan and Aleut populations. An intimate relationship between geography and genetics through Mantel tests was observed for both Siberia (r = 0.55 P > 0.001) and the Aleutian Islands (r = 0.72 P > 0.000). The genetic structure of the populations of the Aleutian Archipelago most closely approximates the isolation-by-distance model. Am. J. Hum. Biol. 19:203–217, 2007. © 2007 Wiley-Liss, Inc.