The North American deserts have become a rich system to explore the history of biotic diversification and the veracity of methods used to reveal structure and test hypotheses. Example 1. Molecular biogeographic approaches have revealed several pervasive Neogene / Quaternary zones of transition between sister lineages within the North American deserts, but important questions remain unanswered about the nature of these zones, e.g, geological, paleoclimatic, and ecological contexts; and temporal complexity. Example 2. Species have responded to Quaternary climatic changes in a variety of ways, and combining genetics with niche modeling has become a popular approach to reconstructing the response. Two emerging issues are considered: first, to what extent, and why from a biotic/ecological trait perspective, do co-distributed species respond in a concerted fashion; and second, what shall we infer when the phylogeographic or landscape genetic and paleo-niche models do not agree?