Pleistocene faunas of the eastern Pacific shelf are characterized by thermally anomalous species assemblages—i.e., coexisting species that inhabit different climatic regimes today. We used data on the latitudinal ranges of 2887 extant molluscan species to determine the biological basis of the Pleistocene faunal migrations. Overall, the species exhibiting the most extensive range shifts (termed extraprovincial species) were not drawn randomly from the available species pool, and the pattern is climatically asymmetrical. The latitudinal ranges of southern extraprovincial species are significantly wider on average than those of the species pool from which they were drawn, but the ranges of northern extraprovincials resemble those of their parent pool. This contrast is primarily a consequence of the biogeographic structure of the eastern Pacific fauna; water-mass boundaries are more effective barriers for southern species migrating north in response to changing climatic conditions than for northern species moving south. Our analysis of Pleistocene marine mollusks provides a biological and environmental context for species response to environmental change and permits predictions about the movement of eastern Pacific species relative to major environmental barriers in the face of future global change.