For waging wars against Heaven and ravaging the Earth in the distant past, the Giants are confined to the icy walls surrounding Cocytus, unable to move, though capable of seeing and breathing. In the game, the Giants try to hinder Dante's progress towards Lucifer by blowing their icy breath towards him. Being exposed to their breath will cause damage and/or knock Dante to his death.
They are not fully seen in the game, but they are seen in the Animated Epic in a brief cameo appearance. In the cameo, they appear as giant (though their exact depiction of their size isn't clear, mainly because it was never shown of Dante encountering them directly), bony creatures with skeletons formed of jagged ice with sharp edges pointing out to signify their limbs. They do have a head and a face, which expresses an evil expression, with downward-pointing diagonal directed eye-spots and a sinister smile, which both light up neon bluish-green in the dark.
- In "Inferno," Virgil mentions that the Giants outside the Circle of Treachery consists of Nimrod, Ephialtes, Antaeus, Briareus, Tityos, and Typhon. Unlike their game and movie counterparts, the Giants are not hostile, and lower the two travelers down into Cocytus to conclude Dante's journey through Hell.
- In Greek myth, the Giants (Gigantes) were a race of creatures who sprung from the Earth as a final challenge to the Olympian gods for control of the world. They stormed Mount Olympus, but were defeated and destroyed by the gods, who sentenced them to Tartarus (a mythological version of Hell).
- Ice Giants, or Frost Giants, are known as an actual race of creatures in Norse mythology. Known as hrimthurs or Rime Giants, they were the children of the primordial giant, Ymir, who was murdered by the chief god, Odin. All giants, including the Frost Giants, were the archenemies of the Aesir, the Norse gods, and were destined to kill them during the Apocalypse. The Frost Giants had their home in the realm of Niflheimr, an icy region which bordered the Norse underworld, Hel.
- Although never explicitly stated, the Giants might be synonymous with the Biblical Nephilim, the enormous offspring of humans and the angelic Watchers of Heaven. Against God's will, these 200 angels descended to Earth and took human women as wives, additionally teaching mankind forbidden arts. Their unholy children grew to alarming size, and devoured everything they could lay hands on, including people. As penalty, the Watchers were captured and imprisoned for eternity in hellish domains, and the corrupt humans and Nephilim were drowned in the Great Flood, of which only the patriarch Noah and his family survived.
- Among the Giants named in the Inferno, Nimrod was actually neither a Biblical giant nor one from Greco-Roman myth. He was infamous for building the Tower of Babel, an affront to God.
- Briareus, also known as Aegeaon, was one of the Hekatonkhieres (the Hundred Handed Ones), the siblings of the Titans and the uncles of the Olympian gods. They were imprisoned by their father, Ouranos, in the Underworld because he thought they were too ugly to be seen. The Hekatonkhieres were later freed by their nephew, Zeus, and fought with him during the Titanomachy. After this war, they were stationed at the gates of Tartarus as guards of the damned.
- Tityos was the giant son of Zeus in Greek mythology. He was so enormous that his mother was split apart when he was born. Tityos was later commissioned by Zeus's wife, Hera, to chase and assault the Titaness Leto, with whom Zeus had an affair and gotten pregnant. Leto was able to find shelther and bore twins: the gods Artemis and Apollo. Not even days old, the twin gods then sought out their mother's assailant and slew Tityos with their arrows. His soul was sentenced to Tartarus, where he is tortured by having his body constantly clawed by vultures.
- Typhon in Greek myth was not a giant but a serpentine monster, an immortal child of Gaia, the Earth. When Zeus defeated the Titans and imprisoned them in the underworld, Gaia gave birth to Typhon as a challenge to Zeus's authority over the universe. Typhon nearly succeeded in destroying the king of the Olympian gods by ripping out his sinews. However, Zeus was rescued by the nymph Styx and was able to drive Typhon underneath a mountain, trapping the creature there. He is said to be the cause of volcanic eruptions on Earth. Before his imprisonment, Typhon had several more monstrous offspring by the nymph Echidna; these children continued to terrorize the country. One of these children was Cerberus.