The Frost Giants first appear laying siege on Asgard, led by Loki, but they are stopped by Thor returning from his battle against the Wrecking Crew on Earth. After defeating the Frost Giants and Loki, Thor and Odin get into an argument due to Thor being busy on Earth instead of protecting Asgard. They don't know that Loki was also behind the Wrecking Crew's attack as part of a manipulative scheme to cause a schism between Thor and Odin.
When the Avengers fight the Masters of Evil and destroy the Norn Stones, Giant-Man and Wasp find themselves transported to Jotunheim. Hank faces the Frost Giants to protect the unconscious Jan, but they use the Casket of Ancient Winters against him. Luckily, the size-shifting heroes are saved by Sif, Brunhilda and the valkyries.
When Loki turns Thor into a frog, the Frost Giants are his henchmen, but they are defeated by Spider-Man and his team with new weapons given by Eitri, the Dwarf king.