The canid subfamily Caninae includes all the living canids and their most recent fossil relatives. Their sister taxon is the Borophaginae with which they share an important modification of the lower carnassial, namely the presence of a bicuspid talonid, which gives this tooth an additional function in mastication. Contributing to this function is the enlargement of the posterolingual cingulum of M1 and development of a hypocone. The Caninae diverged from the Borophaginae in the narrowing and elongation of the premolars separated by diastemata and placed in a shallow ramus and narrow muzzle. These latter features allow the Caninae to be recognized in the fossil record as early as the beginning of the Oligocene (34 Ma) and constitute evidence that they represent a monophyletic group.

In striking contrast to the history of the Borophaginae, the Caninae remain confined to a closely similar group of fox-sized species (Leptocyon spp.) throughout the Oligocene and showing very limited cladogenesis into the end of the medial Miocene (12 Ma), a span that saw marked adaptive divergence in the Borophaginae and the origin of all its major clades. By 12 Ma (beginning of the Clarendonian Land Mammal age) few fox-sized borophagines remained and most of those held hypocarnivorus adaptations. At that point the Vulpini appear both as mesocarnivores (Vulpes spp.) and hypocarnivores (Metalopex spp.) reproducing, on a much smaller scale, the range of adaptations shown in the initial radiation of the Borophaginae.

By the end of the Clarendonian (9 Ma) the first members of the tribe Canini appear. Initially this group was represented by the genus Eucyon, largely by a single widespread North American species E. davisi. Our cladistic analysis predicts that the roots of the South American clade subtribe Cerdocyonina, sister taxon to E. davisi and Canis species (together, subtribe Canina), must also have been present, but taxa representing this group do not appear in the North America record until the earliest Pliocene (latest Hemphillian, 5 Ma). Species of three genera (Cerdocyon, Chrysocyon, and possibly Theriodictis), now confined to South America, appear in the fossil record of the southern United States and northern Mexico prior to and just after the opening of the Panamanian Isthmus (ca. 3 Ma), indicating that important cladogenesis within the South American clade took place in North America. Species of Eucyon make their appearance in the Old World in the late Miocene, and E. davisi has a Pliocene record in Asia. Species of this genus undergo a modest adaptive radiation in Eurasia during the Pliocene.

In the late Miocene and early Pliocene two species of Canis appear in North America (C. ferox and C. lepophagus), representing the initial cladogenesis within the genus. These animals are all coyote-sized and represent a broadening of body size range within a mesocarnivorous dental adaptation. Toward the end of the Pliocene and into the Pleistocene in North America a curious and rare group of jackal-like species (C. thöoides, C. feneus, and C. cedazoensis) seem to form an endemic clade arising near C. lepophagus. These taxa are dentally similar to jackals, especially C. aureus, but sha