As Fullmetal Alchemist: Brotherhood winds its way toward its conclusion, the final showdown between Ed and Father feels inevitable. Ed's victory is far from guaranteed, though, and is put into jeopardy after Father successfully destroys Ed's automail arm. Realizing that his brother will need both arms to defeat Father, Al encourages May — his love interest who's a Xing princess and an expert in alkahestry – to help him perform a transmutation, sacrificing his own soul so that Ed can get his arm back. Al then reunites with his body on the other side of the Gate of Alchemy, and Ed is eventually able to successfully defeat Father. 

Even after Al's sacrifice, though, Ed still needs help to further weaken father. He relies on Greed, one of the Seven Homunculi that embodies Father's greed (or at least a portion of it), who decides to sacrifice himself to turn Father's body into weak charcoal. Ed is then able to punch a hole through Father's chest, releasing the souls of Xerxes that were trapped inside and sending Father through the Gate of Truth, where he is trapped for eternity. 

As everyone mourns Al in the aftermath of Ed's victory, Ed refuses to use a philosopher's stone to try and bring his brother back. Instead, he performs a human transmutation on himself, agreeing to give up his use of alchemy forever in exchange for getting Al back in his original body. Ed's sacrifice means that he'll never be able to perform alchemy again, but it's a sacrifice he's willing to make in exchange for his brother's life.