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Squamates from the Mesozoic of North America have been collected since the end of the nineteenth century. To date, the fossils are known to occur in the Late Jurassic, Aptian-Albian, Cenomanian, Turonian, Santonian, Campanian, and Maastrichtian. Most of the records are from the Western Interior in the arid regions associated with the Rocky Mountains. Geographically, these records extend from central Alberta, Canada, south to northern Mexico. The earliest squamates are primitive forms of scincoideans and anguimorphans from the Late Jurassic-Early Cretaceous. At the beginning of the Late Cretaceous, the squamate fauna in North America changes dramatically to include a much greater diversity of taxa with a mix of lineages now extinct (e.g. Polyglyphanodontini, Chamopsiidae, Contogeniidae) and lineages still alive today (e.g. Anguidae, Xantusiidae, Platynota, Serpentes). The greatest diversity appears to be during the late Campanian, but diversity appears correlated with number of localities sampled and the late Campanian is the best sampled horizon in the Mesozoic of North America. The apparent sudden change in the North American squamate fauna is coincident with similar changes to other vertebrates (mammals, dinosaurs) and the opening of a land bridge with Asia. The lack of taxonomic and systematic study of the squamates from the Early Cretaceous of Asia makes comparison difficult, but it is likely that introduction of Asian taxa into North America was responsible, at least in part, for the relatively rapid change in the North American fauna. The hypotheses of an additional invasion from Asia during the Turonian is not supported, but the hypothesis of a second opening with Asia during the Santonian is weakly supported by the appearance of an iguanian in North America. Additional iguanians from the Campanian may have evolved in situ or may have entered North America from Asia as late as the mid-Campanian. Many of the most conspicuous lizards of the Late Cretaceous (Polyglyphanodontini, Chamopsiidae, paramacellodid-cordylid grade scincoideans) went extinct at the terminal Cretaceous extinction event, while most of the anguimorphans and snakes appear little affected. Amphisbaenians do not appear in North America until after the early Paleocene.