In my dissertation, I explore macroevolutionary trait evolution and diversification of snakes at multiple taxonomic levels. In my first chapter, I use a combined morphological and molecular dataset for the higher clades of snakes and several important fossil lineages to infer the phylogenetic placement of fossil taxa and simultaneously use them to calibrate the phylogeny. I then use this time tree to reconstruct the early evolution of large gape size (followed by multiple losses) and multiple independent instances of limb reduction early in snake history. In my second chapter, I reanalyze the datasets of reproductive mode (i.e., oviparity and viviparity) in squamate reptiles and toepads in geckos to examine the influence that each trait has on rates of speciation and extinction, reconstruct the histories of these traits, and explore the differences between the Hidden State Speciation and Extinction (HiSSE) and Binary State Speciation and Extinction (BiSSE) models. I show that diversification rates have varied considerably across Squamata, with particularly high rates of diversification shown within snakes, and that use of HiSSE models provides less support for reversals from viviparity to oviparity within snakes or other squamates, or for multiple evolutions of toepads in geckos than was obtained previously using the BiSSE model. In my final chapter, I use restriction site associated DNA sequence data to show that the Red Diamond Rattlesnake, Crotalus ruber, is made up of distinct northern and southern populations. Model selection analyses show that these populations were historically genetically isolated, but have since come into secondary contact and are now exchanging genes at relatively high levels. Both divergence and secondary contact are estimated to have occurred during the Pleistocene, suggesting a role for climatic cycling in driving these events and possibly producing similar genetic structure in other taxa. I have provided insight into how traits have evolved across the major clades of snakes, as well as lower-level processes that influence the divergence of local lineages that may or may not eventually become species and contribute to the global snake diversity.