Until recently, the Capreolinae were known as the Odocoileinae - named after the highly-successful genus Odocoileus. Indeed, the white-tailed deer (Odocoileus virginianus) has one of the broadest geographical distributions of any deer, ranging from the Arctic Circle to below the Equator, and is the oldest modern cervid species, indistinguishable from fossils from 3.5 million years ago.

The origins of the Capreolinae are uncertain due to a scarcity of early fossils. However, molecular data indicates that this subfamily likely diverged from the Old World cervid radiation (Cervinae) at some time during the middle Miocene. The earliest known fossil evidence of this subfamily appear in North America and Eurasia around 5 million years ago. Members of the Capreolinae reached South America via the Panama land bridge during the late Pliocene or early Pleistocene, and rapidly evolved into many forms specialized for various niches. Again, the fossil record at this time is scant, but it has been suggested that all South American species are descended from Odocoileus. Recent molecular studies have demonstrated significant complexity in the taxonomy of South American deer. The relationships among these deer, particularly the enigmatic brockets (Mazama, Bisbalus, Passalites, Subulo) are still being elucidated.

Three tribes are generally recognized:

1. Alceini - moose
2. Capreolini - roe deer and water deer
3. Odocoileini - New World deer

The telemetacarpal foot structure is the diagnostic characteristic of this group: the second and fifth metacarpals are present as distal splinters of bone (by the dewclaws). Pedal glands are found in the hind legs of all species, and tarsal glands are always present (if rudimentary). Unlike the Cervinae, the antler cycle includes a pause between when the antlers are shed and when the new pair begins growing.

The anomalous Hydroptes was traditionally thought of as the most primitive of the Cervidae due to the presence of enlarged upper canines and a lack of antlers (the same pattern as in the Tragulidae and Moschidae). The general body plan is similar to that of the musk deer, but skull characters firmly plant the water deer in the family Cervidae. At a time, it was considered a member of its own subfamily (Hydropotinae), but is now known to cluster with Capreolus.