Analysis of the teeth, orbital, and gnathic regions of the skull, and fragmentary postcranial bones provides evidence for reconstructing a behavioral profile of Amphipithecidae: Pondaungia, Amphipithecus, Myanmarpithecus (late middle Eocene, Myanmar) and Siamopithecus (late Eocene, Thailand). At 5–8 kg, Pondaungia, Amphipithecus, and Siamopithecus are perhaps the largest known Eocene primates. The dental and mandibular anatomy suggest that larger-bodied amphipithecids were hard-object feeders. The shape of the mandibular corpus and stiffened symphysis suggest an ability to resist large internal loads during chewing and to recruit significant amounts of muscle force from both the chewing and non-chewing sides of the jaw so as to increase bite force during mastication. The large spatulate upper central incisor of Pondaungia and projecting robust canines of all the larger amphipithecids suggest that incisal food preparation was important. The molars of Siamopithecus, Amphipithecus, and Pondaungia have weak shearing crests. This, and the thick molar enamel found in Pondaungia, suggests a diet of seeds and other hard objects low in fiber. In contrast, Myanmarpithecus was smaller, about 1–2 kg; its cheek teeth suggest a frugivorous diet and do not imply seed eating. Postcranial bones (humerus, ulna, and calcaneus) of a single large amphipithecid individual from Myanmar suggest an arboreal quadrupedal locomotor style like that of howler monkeys or lorises. The humeral head is rounded, proximally oriented, and the tuberosities are low indicating an extremely mobile glenohumeral joint. The great thickness of the midshaft cortical bone of the humerus implies enhanced ability to resist bending and torsion, as seen among slow moving primate quadrupeds. The elbow joint exhibits articular features for enhanced stability in habitually flexed positions, features also commonly found in slow moving arboreal quadrupeds. The short distal load arm of the calcaneus is consistent with, but not exclusive to, slow arboreal quadrupedalism, and suggests no reliance on habitual leaping. A recently recovered talus of an amphipithecid suggests a possibly more active arboreal quadrupedalism.