Grace is a type of divine energy related to an angel's being. It's effectively what makes them angels; without it they are mortal. Anna calls its power "pure creation." Removal of grace is considered a great taboo by angels; it is akin to disobeying orders and punishable by a death sentence, or in the very least torture and imprisonment. Uriel is able to take Anna's grace from the oak tree that it created when she fell. In turn she is able to re-imbibe it and return her angel status.
Metatron takes Castiel's grace from him to use in a spell to cast all the angels from Heaven. Without it, Castiel is human, although much like Anna he was still able to hear the angels on "angel radio." After living as a human for some time, he takes the grace of and angel named Theo before killing him, becoming an angel again. This indicates that grace is not unique to an individual angel, and can be transferred, though Castiel seemed unsure whether taking Theo's grace would be permanent, or what powers he would have. The consequences of stealing another angel's grace were later revealed by Metatron, who told Castiel that his stolen grace was fading, and that once it was used up, Castiel would burn out along with it. Foreign angel grace appears to burn away due to an angel using its powers, as shown with Castiel and later Lucifer. However, an angel's grace can regenerate on its own; as long as even a minuscule amount of the angel's natural grace remains, it will recharge over time.
When angels leave their vessels a small amount of the angel's grace remains inside the vessel. Angel lore says that "the departed shall remain, and the remains shall be the departed." The Men of Letters believed that if the grace could be extracted, it could be used in a tracking spell to locate the angel the grace belonged to. They even created a syringe with the purpose of extracting grace for its use in spells.
Anna Milton reveals that she is an angel who chose to fall from Heaven and ripped out her grace painfully. Witnesses mistook Anna's grace for a shooting star. Where it landed, in Union, Kentucky, an enormous oak tree sprouted in the space of a year. In conversation with Dean, Anna indicates that given the choice she would not recover her grace, and would remain human. She relishes the full range of emotions that humans enjoy and the choices they have.
When Anna arrives, the grace has been stolen from the oak tree, and Uriel reveals to Dean that he has it bottled in a phial he keeps around his neck. It appears as an indistinct white smoke with its own internal source of light. During the climactic fight of the episode, Anna smashes the phial, and the grace surrounds her and enters her mouth, after which her eyes glow yellow and her body glows bright white.
Anna yells for the Winchesters to close their eyes as the light intensifies. In the final flash, Alastair's meatsuit is destroyed, and when the dust settles, Anna has also disappeared. She reappears in future episodes as a fully reconstituted angel.Over the course of season five, Castiel is cut off from Heaven, and by 5.02 Good God, Y'All has lost a number of his angelic powers, including his ability to heal humans. He does not however appear to be any less an angel. In 5.21 Two Minutes to Midnight he has become essentially human (this is also seen with Future!Castiel in the alternate future or alternate universe in 5.04 The End, however no reference is made to his grace or lack of it, though his depowering may have had to do with carving an angel banishing sigil into his chest in 5.18 Point of No Return. His grace is not mentioned when he is restored in 5.22 Swan Song. Following his destruction by the leviathans he takes into himself from Purgatory, he is resurrected and lives with and marries a woman called Daphne Allen for a year, with no memory of who he is. Again it does not appear that he lost his grace.
Metatron removes Castiel's grace to use in the spell to expel all the angels from Heaven. He sends Castiel to Earth saying "I want you to live this new life to the fullest. Find a wife. Make babies. And when you die and your soul comes to Heaven, find me. Tell me your story."
After being held captive and tortured by Malachi, one of his minions, Theo, tries to get Castiel to "put in a good word" with Metatron for him. Castiel slits Theo's throat with an angel blade, releasing his grace. Castiel then inhales it, turning him back into an angel and restoring at least some of his powers which is proven when he is then able to smite the now-human Theo.
Sam and Castiel learn that Sam still has a bit of Gadreel's grace inside of him which, though harmless, could be used to track the angel according to a Men of Letters file "On the Inner Workings of Angels." Castiel's healing of Sam is slowly destroying the grace and if he keeps it up, it will be gone for good. Sam and Castiel start a procedure to extract the grace, but the process causes Sam to start to revert back to the state he was in before Gadreel possessed him. Sam doesn't care and insists Castiel continue as they don't have enough grace for the spell. Castiel reluctantly continues, but stops when he can't stand it anymore and completely heals Sam of the rest of the damage he took from the trials, destroying the rest of the grace. Sam and Castiel try the spell, but find that they didn't have enough grace for it to work.
After Dean attacks Gadreel with the First Blade, Sam and Castiel find the injured angel outside the Bunker, where Castiel proceeds to heal him. When healing Gadreel, Castiel is shown to be slightly weakened by the act.
Hannah approaches Metatron to ask if he used all of Castiel's original grace to perform the ritual to banish the angels. Although Metatron claims that there is a small piece of Castiel's grace left, Castiel interrupts before Hannah can follow that line of inquiry any further, asking Hannah to respect his choice not to extend his life by evil means.
Learning that Sam is attempting to cure the now-demon Dean, Castiel travels to the bunker to aid him, but is beginning to die as his grace runs out. When Castiel and Hannah are attacked by Adina, a rogue angel whose lover was killed in an earlier fight, Crowley intervenes and kills Adina so that Castiel can take her grace, wanting Castiel to deal with the problem of demon Dean one way or the other. Castiel is able to help Sam cure Dean, but the Winchesters are left unaware that he is still running down.
After Castiel and Bobby Singer break Metatron out of Heaven's dungeon, Castiel removes Metatron's grace, rendering him human and mortal in order to have leverage over him in finding out what he knows about a cure for the Mark of Cain. After Sam demonstrates Metatron's new state by shooting him in the leg, Metatron quickly talks. Although unable to offer a cure for the Mark, he reveals that he knows the location of some of Castiel's original Grace, prompting Castiel to take him on a road trip to recover it.
Castiel and Metatron continue their search for Castiel's grace, coming under attack from a cherub along the way. Metatron finally leads Castiel to a library where he had another angel hide the grace. As they search, trying to find the right book, Metatron incapacitates Castiel with a spell and takes the demon tablet, what he had really come for along with the grace. However, Castiel figures out that he needs to find the right quote to find the grace and finds it in Don Quixote. Metatron initially intended to take the grace too, but once Castiel has it, he leaves with what he has. Castiel reabsorbs what was left of his grace and restores some of his power, though his wings are still broken.
When Ambriel finds Amara's motionless body on the forest floor, she approaches it slowly to check if Amara is still alive. Amara's eyes suddenly spring open and she grabs Ambriel by the throat. When Castiel hears this, he rushes to them in time to watch Amara consume Ambriel's grace, spark of life, and memories.
The spell to open a new rift in Apocalypse World requires archangel grace as the key ingredient. Michael proceeds to siphon off Lucifer's grace, leaving some left in Lucifer for a "rainy day." Lucifer's diminished grace leaves him in a weakened state, no longer able to smite people with a snap of his fingers.
Lucifer in his weakened state finds and corners a cherub in an alley and siphons off its grace. Still requiring more, Lucifer asks where he can find angels, but the cherub tells him there aren't many angels left. As the cherub pleads with Lucifer, he is killed when Lucifer drives his fist through the cherub's chest.
Discovering the faith healer Sister Jo is actually an angel named Anael, Lucifer prepares to steal her grace, but Jo convinces him to take small "sips" from her when needed. This stops him from needing to seek out other angels to drain and kill, as well as ensuring Jo's own survival.
In the Needham Asylum, Ketch watches Asmodeus extracting grace from Gabriel and injecting it into his arm. The archangelic grace appears to give him certain special abilities and allows him to overpower Ketch with ease. Asmodeus injects more grace into his arm before leaving him with Gabriel. Ketch decides to rebel against him by rescuing Gabriel, taking the archangel blade, stealing his extracted grace, and retreating to the Men of Letters Bunker.
Ketch offers to relinquish them all to Sam and Dean in exchange for protection from Asmodeus, to which Dean agrees. Having assembled all the ingredients to open an inter-dimensional rift to Apocalypse World, Sam uses the archangel grace to complete the spell and send Dean and Ketch through the portal to search for Mary and Jack.
Preparing for their journey to Apocalypse World, Castiel tells Dean that Gabriel wished to extract his grace in private. When Gabriel arrives, his vial of grace is less than full, but he assures everyone that it is more than enough for the spell to open a rift. As Rowena mixes the grace with the ingredients, a rift appears, but as the group begin to make their way towards it, the rift begins to falter and disappear.
After Gabriel and Rowena magically roofie Lucifer, they take him to the Bunker, where Rowena places a powerful bind on him. Positioning a spell bowl underneath him, Castiel makes an incision on Lucifer's throat, extracting the grace. When Lucifer questions why they didn't just take his grace and kill him at the bar, Sam reveals they plan to slowly drain the grace out of him to keep the rift open for longer than 24 hours.
As the grace continues dripping from his wound, Lucifer begins to taunt Rowena, prompting her to explode at Lucifer and reveal that Jack is in Apocalypse World and doesn't care for him. Having been angered enough to break the binding, Lucifer heals his wound to prevent the loss of any more grace. As he is about to kill Rowena, she uses a defensive spell to send him flying back through the portal into Apocalypse World.
After finding the deceased Sam and resurrecting him, Lucifer reveals that upon entering Apocalypse World, he came across a group of Michael's angels and consumed their grace, helping him regain some of his lost power.
After being rejected by Jack, Lucifer takes the archangel blade and cuts Jack's neck, allowing him to consume most of his grace. With Jack's grace now coursing through his body, Lucifer is able to supercharge his powers, exhibiting golden eyes like Jack's rather than his usual red.
Michael later reveals to Dean and Castiel that, after consuming the grace of a Nephilim, Lucifer would be capable of ending the whole universe if he put his mind to it.