The earliest fossil species of the family date back to the Late Eocene epoch, with earlier origins suspected.

They can also live in many different types of habitats including aquatic, terrestrial, semi-arboreal, arboreal, desert, mountainous forests, semi-fossorial, and brackish waters.

[3][5][6] Some colubrids are described as opisthoglyphous (often simply called "rear-fanged"), meaning they possess shortened, grooved "fangs" located at the back of the upper jaw.

It is thought that opisthoglyphy evolved many times throughout the natural history of squamates[5] and is an evolutionary precursor to the larger, frontal fangs of vipers and elapids.

[4] Characteristics of Colubridae include limbless bodies, left lung that is reduced or absent with or without a tracheal lung, well-developed oviducts, premaxillaries that lack teeth, maxilaries oriented longitudinally with teeth that are solid or grooved, mandible without a coronoid bone, dentary that has teeth, only a left carotid artery, intracostal arteries arising from the dorsal aorta every few trunk segments, no cranial infrared receptors occurring in pits or surface indentations, and optic foramina that typically traverse the frontal–parietal–parasphenoid sutures.

The oldest colubrid fossils are indeterminate vertebrae from Thailand and specimens of the genus Nebraskophis from the U.S. state of Georgia, both from the Late Eocene.