Non-human primates were once common in North America during the early and middle Eocene (55 to 48 million years ago). One North American Eocene primate family is the Notharctidae, animals similar to living lemurs now only found on Madagascar. Three early Eocene genera and two common middle Eocene genera of notharctines are presently known from North American. This proposal addresses a major issue concerning the history of these animals, the relationships of the middle Eocene genera Notharctus and Smilodectes. Despite being represented by some of the most complete skeletons of fossil primates known, no consensus has developed regarding the origin of these genera nor have their relationships ever been fully established, either with one another or with other North American notharctines. In order to more fully understand the relationships of Smilodectes and Notharctus it is necessary to document changes in transitional notharctines across the early to middle Eocene boundary. A careful analysis of the relationships of these notharctines with the Asian primate Pondaungia (once considered an anthropoid, now a potential notharctine) and with the more recently described possible anthropoid Siamopithecus from Thailand may shed light on notharctid relationships with anthropoids, the group that includes all living monkeys, apes, and humans.