Fullmetal Alchemist is a science fantasy manga set in the early 20th century in a country called Amestris in an alternate-historical Earth with technology dating from early 20th century Europe. In this alternate world, the exaggerated science of alchemy is heavily used in conjunction with acretian soul wanderers, but takes on a further fantastic element not seen in real-life alchemy. In the fictional world of the series, alchemy is the science of transmuting matter into a different form of that same matter (following the law of equivalent exchange) through the use of transmutation circles—based on real-world science, yet also magical, with seemingly infinite uses. Talented alchemists may apply to take a State Alchemist test to join the Amestris military's State Alchemists.
Edward and Alphonse Elric were brothers living in the village of Resembool in the country of Amestris. Their father Hohenheim (Hohenheim of Light in the anime, Van Hohenheim in the manga) left home when Edward and Alphonse were still very young. Years later, their mother, Trisha Elric, died of a terminal illness. After their mother's death, Edward becomes determined to bring her back through the use of alchemy. However, this attempt failed, ultimately resulting in the loss of Edward's left leg and Alphonse's entire body. In a desperate effort to save his brother, Edward sacrificed his right arm to affix his brother's soul to a suit of armor. After that, Edward's left leg and right arm were fitted with two sets of automail, a type of advanced prosthetic limb.
A State Alchemist named Roy Mustang arrives during the failed human transmutation. After seeing their skill at alchemy, Mustang suggested that the way for the two boys to achieve their goals would be to become State Alchemists and work for him. Spurred on by the man's proposal, Edward set out to become a State Alchemist, enabling him to use the resources available to State Alchemists to discover a way to restore what he and Alphonse had lost. The brothers eventually learn of the Philosopher's Stone and set off in search of it as a means to restore their bodies. Along the way they discover secrets about the Philosopher's Stone they never wanted to know, and find others who seek it as well, doing almost whatever they can to get their hands on it.
The stories of the manga and anime separate soon after the encounter with Greed, and weave vastly different tales. The most prominent of the differences is the primary antagonist. In the manga, this is a man known simply as "Father". Father is the creator of all the homunculi in the manga series and commands them from behind the curtains of the High Command of the country Amestris. It is suspected that Father plans to use Amestris as a gigantic transmutation circle to create a Philosopher's Stone, but the homunculus Envy hints that, although close, this is not the whole truth.
Father's counterpart in the anime is a woman called Dante, a former lover of Hohenheim. Centuries ago, the two were masterful alchemists and perfected methods for making the Philosopher's Stone and a form of immortality in which they use others' bodies until they age. Hohenheim eventually fell in love with another and left Dante, taking with him the perfected Philosopher's Stone formula. Although Dante is still able to jump from body to body to cheat death over the centuries, she is able to spend less and less time in each body as it decays faster with each jump, and each jump results in the stone she possesses to lose its power over time. Though Dante did not create all of the Homunculi, she sustains them by feeding them imperfect shards of the Philosopher's Stone. She uses them to spur Edward and Alphonse, along with other Alchemists as desparate as they are, into creating another complete Philosopher's Stone for her.