The cure for vampirism is an old Campbell family recipe. The only known ingredients are garlic, sage, and the blood of the sire vampire. The cure is also dependent on the turned not drinking any human blood, as ingesting even a single drop will make the vampirism permanent and irreversible. The cure itself has a pungent smell and taste. Once the cure takes hold, the turned will begin painfully projectile vomiting the vampire's blood from their system until they pass out, later waking a human once more. The cure also leaves them sick for a few days as any remaining traces of vampirism are purged from their system.
After Dean gets turned into a vampire by Boris, Samuel Campbell reveals that there is a cure -- what Samuel calls "an old family recipe." Samuel states that the cure hasn't been tried since "God knows" and it is described in his grandfather's journal. He warns that the two most important components for the cure depend on Dean: He cannot drink even a single drop of human blood or the cure won't work, and he must collect the blood of his sire, Boris. After Dean leaves, Samuel displays suspicions as he had previously informed Sam of the cure. Sam claims that Samuel must've told someone else.
After Dean slaughters Boris's nest, the Winchesters and Samuel are able to bring the cure together and Dean drinks it. After vomiting up a large quantity of blood, Dean experiences flashbacks of his time as a vampire before becoming human once more. However, the flashbacks show Dean that Sam seemingly allowed him to be turned.
Dean remains suspicious that Sam allowed him to be turned by Boris and tries to use Veritas' truth curse to find out the truth. After Veritas reveals that Sam can lie even under the curse, Sam admits that he did allow Dean to be turned as he knew about the cure.
After finding a young woman who has recently been changed into a vampire by Seth, Dean stops Aiden, Josephine Barnes, and Krissy Chambers from killing her. Dean tells the young hunters that as the young woman has not yet fed, they can cure her if they can get Seth's blood.
After Seth is taken down by Krissy, the Winchesters create the cure for the young woman which is given to her by Aiden and Josephine.
Following the deaths of her "sons" Cody and Dale, Celia changes her "daughter" Alex Jones into a vampire. However, Alex does not feed before the Winchesters and Jody Mills raid the nest. After Jody kills Celia with Alex's help, the Winchesters are able to cure her using Celia's blood. Dean warns that the cure will make Alex sick for a few days and she indeed displays some signs of fever as the cure performs its work on her.
After discovering that Officer Doug Stover has been changed into a vampire, Dean tells Sheriff Donna Hanscum that as Doug has just been changed, he has not yet fed and thus he can be cured. As Dean describes the cure to Donna, Doug's sire, Marlon, appears and reveals that his blood is the last ingredient. Donna kneecaps Marlon with a shotgun in order to get information on Agent Terrance Clegg's location from him. As she demands answers, Donna orders Dean to collect Marlon's blood and to mix the cure.
Later, in the Impala, Donna feeds the unconscious Doug the vampire cure. Donna asks if it will really work and Dean assures Donna that the cure had previously worked on Dean himself. When Doug regains consciousness, he is human once more.