Recent computational and methodological advances in phylogenetics and bioinformatics, along with the increasing availability of evolutionary and ecological data, have produced deeper insights into the evolutionary history of mammals. This is particularly relevant for understanding the geography of mammalian diversity in the Neotropics, home to a quarter of the world’s mammals, an understanding that requires broad knowledge of lineages, their spatial distributions, and the history of the areas they have occupied since the Mesozoic. This chapter provides an up-to-date overview of the way in which recent research that incorporates model-based approaches and phylogenetically informed analyses has driven changes in regionalization schemes, rewritten existing thoughts about ecogeographic principles, and ultimately contributed to a better explanation of the current distribution of mammals in the Neotropics. This section concludes with perspectives about potential future studies needed to fill gaps in what is known about mammalian biogeography in this remarkably diverse realm.