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Group of squamate reptiles
Automatic taxobox
| name = Ophidians
| fossil range = Middle Jurassic – Holocene,) is a group of squamate reptiles including modern snakes and reptiles more closely related to snakes than to other living groups of lizards. Ophidia was defined as the "most recent common ancestor of Pachyrhachis and Serpentes (modern snakes), and all its descendants" by Lee and Caldwell (1998: 1551). The latter author has used Ophidia in a manner inconsistent with this definition, using it to incorporate other more basal stem snakes, such as the Late Cretaceous Najash rionegrina or the Jurassic Diablophis and Portugalophis. The clade name Ophidia derives from the Ancient Greek word ὀφίδιον , meaning "small snake".

Modern snakes are thought to have evolved from either burrowing or aquatic lizards during the mid Cretaceous period, and the earliest known fossils date to around 112 Ma ago. However, the relationship between modern snake and more primitive snake ancestors, many of which retained hind limbs, is less clear. While many of these "stem snakes" are known from Mesozoic fossils, some of them may be descendants of the earliest true snakes rather than more primitive lineages. Below is a cladogram modified from a study by Wilson et al. (2010), which found many stem snakes of other studies to be true snakes instead. Below is different phylogenetic overview of ophidians, following the study by Caldwell et al. 2015. The fossil record of snakes is relatively poor because snake skeletons are typically small and fragile, making fossilization uncommon. Fossils readily identifiable as snakes (though often retaining hind limbs) first appear in the fossil record during the Cretaceous period. The earliest known snake fossils come from sites in Utah and Algeria, represented by the genera Coniophis and Lapparentophis, respectively. These fossil sites have been tentatively dated to the Albian or Cenomanian age of the late Cretaceous, between 112 and 94 Ma ago. However, an even greater age has been suggested for one of the Algerian sites, which may be as old as the Aptian, 125 to 112 Ma ago. Based on comparative anatomy, there is consensus that snakes descended from lizards. Pythons and boas—primitive groups among modern snakes—have vestigial hind limbs: tiny, clawed digits known as anal spurs, which are used to grasp during mating. An early fossil snake, Najash rionegrina, was a two legged burrowing animal with a sacrum, and was fully terrestrial. One extant analog of these putative ancestors is the earless monitor Lanthanotus of Borneo (though it also is semiaquatic). Subterranean species evolved bodies streamlined for burrowing, and eventually lost their limbs.

Many researchers believe that snakes share a common marine ancestry with mosasaurs, a suggestion advanced in 1869 by Edward Drinker Cope, who coined the term Pythonomorpha to unite them. The idea lay dormant for more than a century, to be revived in the 1990s. The mosasaurs were aquatic varanid lizards from the Cretaceous—which in turn are derived from Aigialosaurids. According to this hypothesis, the fused, transparent eyelids of snakes are thought to have evolved to combat marine conditions (corneal water loss through osmosis), and the external ears were lost through disuse in an aquatic environment. This ultimately led to an animal similar to today's sea snakes. In the Late Cretaceous, snakes recolonized land, and continued to diversify into today's snakes. Fossilized snake remains are known from early Late Cretaceous marine sediments, which is consistent with this hypothesis; particularly so, as they are older than the terrestrial Najash rionegrina. Similar skull structure, reduced or absent limbs, and other anatomical features found in both mosasaurs and snakes led to a positive cladistical correlation, and some of these features are shared with varanids. The cladogram below, based on Palci and Caldwell (2010), suggests that snakes are more closely related to Dolichosaurids than mosasaurs proper. placing the Dolichosauridae as a sister group to modern snakes and their closest ancestors.