Arboreal primates have distinctive intrinsic hand proportions compared with many other mammals. Within Euarchonta, platyrrhines and strepsirrhines have longer manual proximal phalanges relative to metacarpal length than colugos and terrestrial tree shrews. This trait is part of a complex of features allowing primates to grasp small-diameter arboreal substrates. In addition to many living and Eocene primates, relative elongation of proximal manual phalanges is also present in most plesiadapiforms. In order to evaluate the functional and evolutionary implications of manual similarities between crown primates and plesiadapiforms, we measured the lengths of the metacarpal, proximal phalanx, and intermediate phalanx of manual ray III for 132 extant mammal species (n = 702 individuals). These data were compared with measurements of hands in six plesiadapiform species using ternary diagrams and phalangeal indices. Our analyses reveal that many arboreal mammals (including some tree shrews, rodents, marsupials, and carnivorans) have manual ray III proportions similar to those of various arboreal primates. By contrast, terrestrial tree shrews have hand proportions most similar to those of other terrestrial mammals, and colugos are highly derived in having relatively long intermediate phalanges. Phalangeal indices of arboreal species are significantly greater than those of the terrestrial species in our sample, reflecting the utility of having relatively long digits in an arboreal context. Although mammals known to be capable of prehensile grips demonstrate long digits relative to palm length, this feature is not uniquely associated with manual prehension and should be interpreted with caution in fossil taxa. Among plesiadapiforms, Carpolestes, Nannodectes, Ignacius, and Dryomomys have manual ray III proportions that are unlike those of most terrestrial species and most similar to those of various arboreal species of primates, tree shrews, and rodents. Within Euarchonta, Ignacius and Carpolestes have intrinsic hand proportions most comparable to those of living arboreal primates, while Nannodectes is very similar to the arboreal tree shrew Tupaia minor. These results provide additional evidence that plesiadapiforms were arboreal and support the hypothesis that Euarchonta originated in an arboreal milieu.