In a way, the word megafauna (Greek for "giant animals") is rather misleading--after all, the dinosaurs of the Mesozoic Era were nothing if not megafauna, but this word is more often applied to the giant mammals (and, to a lesser extent, the giant birds and lizards) that lived anywhere from 40 million to 2,000 years ago. More to the point, giant prehistoric animals that can claim more modestly sized descendants--such as the Giant Beaver and the Giant Sloth--are more likely to be placed under the megafauna umbrella than unclassifiable, plus-sized beasts like Chalicotherium or Moropus. (See a gallery of giant megafauna pictures and 10 Giant Mammals that Succeeded the Dinosaurs.)
Now that that technical detail is out of the way, it's also important to remember that mammals didn't "succeed" the dinosaurs--they lived right alongside the tyrannosaurs, sauropods and hadrosaurs of the Mesozoic Era, albeit in tiny packages (most Mesozoic mammals were about the size of mice, but a few were comparable to giant house cats). It wasn't until about 10 or 15 million years after the dinosaurs went extinct that these mammals started evolving into giant sizes, a process that continued (with intermittent extinctions, false starts and dead ends) well into the last Ice Age.
The Giant Mammals of the Eocene, Oligocene and Miocene Epochs
The Eocene epoch, from 55 to 33 million years ago, witnessed the first plus-sized herbivorous mammals. The success of Coryphodon, a half-ton plant-eater with a tiny, dinosaur-sized brain, cam be inferred by its wide distribution across early Eocene North America and Eurasia. But the megafauna of the Eocene epoch really hit its stride with the larger Uintatherium and Arsinoitherium, the first of a series of "-therium" (Greek for "beast") mammals that vaguely resembled crosses between rhinoceroses and hippopotamuses. (The Eocene, by the way, also gestated the first prehistoric horses, whales, and elephants.)
Wherever you find large, slow-witted plant-eaters, you'll also find the carnivores that help keep their population in check. In the Eocene, this role was filled by the large, vaguely canine creatures called mesonychids (Greek for "middle claw"). The wolf-sized Mesonyx and Hyaenodon are often considered ancestral to dogs (even though they occupied a different branch of mammalian evolution), but the king of the mesonychids was the gigantic Andrewsarchus, at 13 feet long and one ton the largest terrestrial carnivorous mammal that ever lived (Andrewsarchus was rivaled in size only by Sarkastodon--yes, that's its real name--and the much later Megistotherium).
The basic pattern established during the Eocene epoch--large, dumb, herbivorous mammals preyed on by smaller but brainier carnivores--persisted into the Oligocene and Miocene, 33 to 5 million years ago. The cast of characters was a bit stranger, featuring such brontotheres ("thunder beasts") as the gigantic, hippo-like Brontotherium and Embolotherium, as well as difficult-to-classify monsters like Indricotherium, which looked (and probably behaved) like a cross between a horse, a gorilla, and a rhinoceros. The largest non-dinosaur land animal that ever lived, Indricotherium weighed as much as 40 tons, making adults pretty much immune to predation by contemporary saber-toothed cats.
The Megafauna of the Pliocene and Pleistocene Epochs
Giant mammals like Indricotherium and Uintatherium haven't resonated with the public as much as the more familiar megafauna of the Pliocene and Pleistocene epochs. This is where we encounter fascinating beasts like Castoroides (the Giant Beaver) and Coelodonta (the Woolly Rhino), not to mention mammoths, mastodons, the giant cattle ancestor known as the Auroch, the giant deer Megaloceros, the Cave Bear, and the biggest saber-toothed cat of them all, Smilodon. Why did these animals grow to such comical sizes? Perhaps a better question to ask is why their descendants are so tiny--after all, svelte beavers, sloths and cats are a relatively recent development. (All kidding aside, it may have something to do with the prehistoric climate, or a strange equilibrium that prevailed between predators and prey).
No discussion of prehistoric megafauna would be complete without a digression about South America and Australia, island continents that incubated their own strange array of huge mammals (until about three million years ago, South America was completely cut off from North America). South America was the home of the three-ton Megatherium, the Giant Sloth, as well as such bizarre beasts as Glyptodon (a prehistoric armadillo the size of a Volkswagen Bug) and Macrauchenia, which can best be described as a horse crossed with a camel crossed with an elephant.
Australia, millions of years ago as today, had the strangest assortment of giant wildlife on the planet, including Diprotodon (the Giant Wombat), Procoptodon (the Giant Short-Faced Kangaroo) and Thylacoleo (the Marsupial Lion), as well as non-mammalian megafauna like Bullockornis (better known as the Demon Duck of Doom), the giant turtle Meiolania, and the giant monitor lizard Megalania (the largest land-dwelling reptile since the extinction of the dinosaurs).
The Extinction of the Giant Mammals
Although elephants, rhinoceroses and assorted large mammals are still with us today, most of the world's megafauna died off anywhere from 50,000 to 2,000 years ago, an extended demise known as the Quaternary Extinction Event. Scientists point to two main culprits: first, the global plunge in temperatures caused by the last Ice Age, in which many large animals starved to death (herbivores from lack of their usual plants, carnivores from lack of their usual herbivores), and second, the rise of the most dangerous mammals of them all--humans.
It's still unclear to what extent the Woolly Mammoths, Giant Sloths, and other mammals of the late Pleistocene epoch succumbed to hunting by early humans--this is easier to picture in isolated environments like Australia than across the whole extent of Eurasia. Some experts have been accused of overstating the effects of human hunting, while others (perhaps with a view to endangered animals today) have been charged with undercounting the number of Mastodons the average stone-age tribe could bludgeon to death. Pending further evidence, we may never know for sure.