In this world there exist alchemists, people who study and perform the art of alchemical transmutation—to manipulate objects and transform one object into another. They are bounded by the basic law of alchemy: in order to gain something you have to sacrifice something of the same value.

The main character is the famous alchemist Edward Elric—also known as the Fullmetal Alchemist—who almost lost his little brother, Alphonse, in an alchemical accident. Edward managed to attach his brother's soul to a large suit of armor. While he did manage to save his brother's life, he paid the terrible price of his limbs.

To get back what they've lost, the brothers embark on a journey to find the Philosopher's Stone that is said to amplify the powers of an alchemist enormously. However on the way, they start uncovering a conspiracy that could endanger the entire nation, and they realize the misfortunes brought upon by the Philosopher's Stone.

Fullmetal Alchemist: Brotherhood is a re-telling of the story from the manga point of view.