The genus _Conophis_ is known only from the Recent. Except that _Conophis_ belongs to the subfamily xenodontinae and probably is of New World origin, little is known about the relationships of the genus. Auffenberg (1958) described a new genus and species of fossil colubrid snake from the Miocene of Montana as _Dryinoides oxyrhachis_ and compared it with several recent genera. This specimen, of which there is a relatively complete skull and a series of vertebrae, seems most closely to resemble a specimen of _Conophis lineatus dunni_ (UF 7657) from Honduras, with which it was compared in basic osteology. The two genera could be related, for the progenitors of _Conophis_ possibly inhabited much of North America in the Miocene.
Another possibility is that the main stock of the xenodontines reached South America in earliest Tertiary times, and that the formation of the Panamanian and Colombian seaways that separated South America and Central America from the Late Paleocene to the middle of the Pliocene left the _Conophis_ stock isolated in Middle America where members of the genus dispersed through semi-arid habitats.
Turning our attention now to the species within the genus, instead of the genus as a whole, _Conophis vittatus_ is readily set apart from other members of the genus on the basis of the universal presence of seven supralabials. In basic coloration it also differs, having no stripe on the 1st scale-row, or spots on the venter, and a maximum of four broad stripes on the body. The other species appear to be more closely related; these make up the _C. lineatus_-group. _Conophis nevermanni_ differs so much from the other species that it might be placed in a separate group. Nevertheless, the basic striped pattern, which is masked by the increased melanism of many specimens, indicates that _nevermanni_ is more closely related to the _lineatus_-group than to _vittatus_. The _lineatus_-group, thus, consists of _pulcher_, _nevermanni_ and the three subspecies of _lineatus_. In this group the color pattern is characterized by the high frequency of ventral spotting, darkening of part of the supralabials, dark pigmentation on the 1st scale-row, and more than four dark stripes on the body of adults. _Conophis lineatus concolor_, on which the dark pigmentation on the body apparently is secondarily lost, is an exception.