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 (Amesutorisu?), 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. They research Human Transmutation, a forbidden art in which one attempts to create or modify a human being. However, this attempt fails, ultimately resulting in the loss of Edward's left leg and Alphonse's entire body. In a desperate effort to save his brother, Edward sacrifices his right arm to affix Alphonse's soul to a suit of armor. Some days later, an alchemist named Roy Mustang visits the Elric brothers, and he tells Edward to become a member of the State Military of the country to find a way to recover their bodies. After that, Edward's left leg and right arm are replaced with automail, a type of advanced prosthetic limb, created for him by his close family friends Winry Rockbell and her grandmother Pinako.
Edward sets out to become a State Alchemist (Kokka Renkinjutsushi?), an alchemist employed by the State Military of Amestris, which infamously annihilated much of the neighboring country of Ishbal's population in the past decade. Becoming a State Alchemist enables Edward to use the extensive resources available to State Alchemists, but it also turns him into what they call a "dog of the military". His more friendly relationship with Roy Mustang however, whom he reports to and who recruited him, allows the brothers freedom to search for the Philosopher's Stone as part of Edward's research, as each State Alchemist is expected to independently research new things which may be of a use to the State Military of Amestris. The brothers set off in search of the Philosopher's Stone as a means to restore their bodies. Throughout their journey, they meet many antagonists, including those who are willing to do anything to obtain the Philosopher's Stone; Scar, one of the few surviving Ishbalans, who seeks vengeance on the State Alchemists for the destruction of his race; and the homunculi, a group of human-like creatures who carry pieces of the Philosopher's Stone inside themselves, and from it derive the ability to survive almost any harm.