The Paul and Irma Milstein Hall of Advanced Mammals is one of two halls in the Lila Acheson Wallace Wing of Mammals and Their Extinct Relatives, which together tell of the great diversification and sudden extinctions of this group of animals. The roots of the mammalian line reach back almost 300 million years, but the mammals featured in this hall, including both primitive and advanced species, arose after the extinction of the non-avian dinosaurs.

The Milstein Hall of Advanced Mammals features extinct mammal relatives such as mammoths, mastodons, saber-toothed cats, camels, and giant ground sloths, which roamed North America until about 10,000 years ago. These species became extinct, possibly due to climate changes at the end of the last ice age, hunting by humans, and infectious disease.

This hall also includes mammals with such modern traits as the hoof, a stirrup-shaped ear bone, and eye sockets near the snout, as well as traits found in primitive mammals: the synapsid opening in the skull, three middle ear bones, and the placenta. Among the animals represented are bats, rodents, rabbits, cats, seals, bears, primates, deer, horses, whales, and elephants.