According to an old legend, when the end of the world comes, Paradise will appear; however, only wolves will know how to find it. Although wolves are believed to have been hunted to extinction nearly two hundred years ago, they still exist, surviving by taking human form.

In the distant future, Mankind has colonized space (with clusters of space colonies at each of the five Earth-Moon Lagrange points), and, down on the Earth, the nations have united as the United Earth Sphere Alliance. However, the Alliance oppresses the colonies with its military power. The colonies desire a peaceful resolution to the situation, joining together in a movement headed by the pacifist Heero Yuy. In the year After Colony 175, Yuy is shot dead by an assassin (believed to be Odin Lowe), forcing the colonies to search for other paths to peace. The assassination also prompts five disaffected scientists from the Organization of the Zodiac, much more commonly referred to as OZ, to turn rogue after the completion of the mobile suit prototype Tallgeese.

Edward and Alphonse Elric are two alchemist brothers searching for the legendary Philosopher's Stone, a powerful object which would allow them to recover their bodies (which were lost in an attempt to bring their mother back to life through alchemy). Born in the village of Resembool from the country of Amestris, the two brothers live there with their parents. Their father, Hohenheim, leaves home for unknown reasons and years later, their mother, Trisha Elric, dies of a terminal illness leaving the Elric brothers alone. After their mother's death, Edward becomes determined to bring her back through the use of alchemy, an advanced science in which objects can be created from raw materials.

Early X-Men issues introduced the team's arch enemy Magneto and his Brotherhood of Mutants featuring Mastermind, Quicksilver, Scarlet Witch, and the Toad. The cast of this comic book series entered the scene focusing on a common human theme of good versus evil and later included storylines and themes about prejudice and racism. The evil side in the fight was shown in human form and under some sympathetic beginnings via Magneto, a character who was later revealed to have survived Nazi concentration camps only to pursue a hatred for all 'normal' mankind. His key followers, Quicksilver and the Scarlet Witch, were Roma (gypsies). Only one new member of the X-Men was added, Mimic/Calvin Rankin, but soon left due to his temporary loss of power.