Issue #27 featured a story called "The Man in the Anthill" about a scientist named Hank Pym who shrinks himself down to insect size and has some adventures. The story gained such acclaim with readers that Pym returned in #35, this time as a more fully-fledged superhero (this was when Marvel was just gearing up its superhero line; Spider-Man had first appeared just the previous month) with a costume and the new name of Ant-Man. Pym would go on to be one of Marvel's more active heroes, over time taking on different guises such as Giant Man, Yellowjacket, etc.
Issue #59 would feature Giant Man taking on the green-skinned monster called the Hulk, and it would usher in a long tenure for that character in the title. Although Giant Man would fade out (to spend more time in the Avengers title), the Hulk would stay with Tales To Astonish until the end of its run with issue #101. The Sub-Mariner would appear in half of the book beginning with issue #70, and the series would be split between Hulk and Sub-Mariner for the remainder of its existence.