Repeated glacial events during the Pleistocene fragmented and displaced populations throughout the northern continents. Different models of the effects of these climate-driven events predict distinct phylogeographic and population genetic outcomes for high-latitude faunas. The role of glaciations in (i) promoting intraspecific genetic differentiation and (ii) influencing genetic diversity was tested within a phylogeographic framework using the rodent Microtus oeconomus. The spatial focus for the study was Beringia, which spans eastern Siberia and northwestern North America, and was a continental crossroads and potential high arctic refugium during glaciations. Variation in mitochondrial DNA (cytochrome b and control region; 214 individuals) and nuclear DNA (ALDH1 intron; 63 individuals) was investigated across the Beringian region. Close genetic relationships among populations on either side of the Bering Strait are consistent with a history of periodic land connections between North America and Asia. A genetic discontinuity observed in western Beringia between members of a Central Asian clade and a Beringian clade is geographically congruent with glacial advances and with phylogeographic discontinuities identified in other organisms. Divergent island populations in southern Alaska were probably initially isolated by glacial vicariance, but subsequent differentiation has resulted from insularity. Tests of the genetic effects of postglacial colonization were largely consistent with expansion accompanied by founder effect bottlenecking, which yields reduced diversity in populations from recently deglaciated areas. Evidence that populations in the Beringian clade share a history of expansion from a low-diversity ancestral population suggests that Beringia was colonized by a small founder population from central Asia, which subsequently expanded in isolation.