Unionidae is a species-rich family of large freshwater mussels with an almost worldwide distribution. In many regions of the world, these mussels are imperiled. Northern Asia, excluding the Far East, is an excellent example of a region with a sharply impoverished fauna of the Unionidae as recently thought with one native species. Since the end of the 19th century, two freshwater mussel species of the genus Unio (U. pictorum and U. tumidus) were repeatedly recorded in Siberia. In the course of this study, these finds are confirmed both morphologically and genetically, the number of known occurrences of these mussels in the waterbodies of Asiatic Russia and Kazakhstan has drastically increased, and the third species, globally endangered U. crassus, was found in the Ob’ River basin. The unique U. tumidus haplotype discovered from the Upper Irtysh River basin is of probable relic origin, which may indicate the presence of a Pleistocene refugium there. Due to natural environmental changes during the last century, several genera of freshwater Mollusca that previously inhabited Western Siberia, but went completely extinct in the Pleistocene, have started to recover the North Asiatic part of their former ranges. The case of Unio is exceptional since the recovery of its lost range goes not exclusively with the humans’ help but also involves the natural mechanisms of dispersal and range extension, and also because these mussels are disappearing in other parts of the world and are placed in the IUCN Red List of Threatened Species.