We summarize the results of a field and laboratory research program (1999–2006) in the Aleutian Islands on the origins of the inhabitants of the archipelago and the genetic structure of these populations. The Aleuts show closest genetic affinity to the contemporary Siberian Eskimos and Chukchi of Chukotka and differ significantly from the populations of Kamchatka (the terminus of the archipelago) and Alaskan Eskimos. Our findings support the hypothesis that the ancestors of the Aleuts crossed Beringia and expanded westerly into the islands approximately 9,000 years ago. The Monmonier algorithm indicates genetic discontinuity between contemporary Kamchatkan populations and western Aleut populations, suggesting that island hopping from Kamchatka into the western Aleutian Islands was highly unlikely. The primary determinant of the distribution of genes throughout the archipelago is geography. The most intimate relationship exists between the genetics (based on mtDNA sequences and intermatch/mismatch distances) and geographic distances (measured in kilometers). However, the Y-chromosome haplogroup frequencies are not significantly correlated with the geography of the Aleutian Islands. The underlying patterns of precontact genetic structure based on Y-chromosome markers of the Aleut populations is obscured because of the gene flow from Russian male colonizers and Scandinavian and English fishermen. We consider alternative theories about the peopling of the Americas from Siberia. In addition, we attempt a synthesis between archaeological and genetic data for the Aleutian Islands.