The extinct organisms can provide crucial information about the origin and time of origination of extant groups. Development of phylogenetic methods for the study of evolutionary processes through time have revolutionized the field of evolutionary biology and resulted in an unprecedented expansion of our knowledge about the tree of life. These methods have shed light on the macroevolution of many taxonomic groups. Despite the increase of studies addressing the diversification patterns of organisms, no synthesis has addressed the case of the most diversified mammalian clade: the Rodentia. The most important subfamily of rodents is the Murinae (Old World mice and rats). Their outstanding diversity, combined with the richness of their fossil record, makes them the best suitable model to study the factors that promote morphological diversity and trigger evolutionary radiations, which are key components of the great tree of life. An essential question in evolutionary biology is to understand the processes that drive high diversity of some clades. Are they linked to the appearance of key innovations or to environmental and biogeographic changes? This project aims by new numerical comparative phylogenetic methods to unravel for the first time the relationships of this important group of rodents. This will provide not only the key means of clock calibration but also the knowledge of the mechanism underlying the origin of novelties in this group. The results will demonstrate the importance of cladistic analyses including extant and extinct members of a clade to accurately calibrate phylogenies and to explore the correlation between phenotypic innovations, biogeographic events, climatic changes and diversification inside this group. Resolving the phylogeny of the Murinae will greatly benefit such diverse fields as Old World biogeography, biodiversity, mammalian paleontology, mammalian molecular-clock studies, and even virology, immunology, and related biomedical fields.