The story of whales is one of the best-documented transitions in evolutionary biology. Living about 50 million years ago along the shallow coastal margins of what is now Pakistan and India, Pakicetus was a wolf-sized, four-legged terrestrial carnivore. The ear bones and tooth structure of its skull tie it to the artiodactyls (even-toed ungulates) — specifically a lineage distantly related to today's hippopotamus. Pakicetus walked on land and could enter the water to hunt; its primary habitat, however, remained terrestrial.

The following millions of years brought transitional forms like Ambulocetus (~49 Mya — 'walking whale') and Rodhocetus (~47 Mya). In these animals the hind legs shortened markedly, the tail grew powerful, and the nostrils began to migrate up the skull. By about 40 million years ago, members of the Protocetidae had reached body plans that spent most of their lives in the water but could still give birth ashore. Basilosaurus (~38–34 Mya), reaching 18 metres in length, was a fully marine mammal that had left land behind entirely; its hind legs had shrunk to a few-centimetre vestige, and its body had become serpentine and streamlined.

By the early Oligocene (~34 Mya), the two great branches of modern whales — the toothed whales (Odontoceti) and the baleen whales (Mysticeti) — had diverged. The baleen strategy of straining food through fibrous plates evolved alongside the increasingly plankton-rich oceans of the late Oligocene and Miocene, eventually producing the ancestors of the largest animal Earth has ever seen, the modern blue whale. Whales offer one of the most striking proofs that vertebrate evolution is not a one-way road: a lineage that once came onto land can, given the right conditions, return to the sea.