"Yes", as attributed to assenting to an angelic being, is the way an angel is allowed to possess a human. It was a critical issue for Dean and Sam, who were the predestined vessels of Michael and Lucifer during the Apocalypse.
- The Rapture - Castiel converses with Jimmy Novak to get him to become his vessel and he eventually says Yes in exchange for the angels protecting his family. Later, his daughter Claire apparently says Yes to Castiel, presumably to save her family, as he is able to briefly possess her. While Jimmy doesn't outright say Yes again to Castiel, his insistence that Castiel takes him as a vessel again to spare his daughter is apparently enough.
- Sympathy For the Devil - Talked about by Zachariah, who tells Dean to say Yes to Michael. Dean says the answer is No. Zachariah tries to torture him and Sam into compliance, but is forced to flee when Castiel shows up.
- Free To Be You And Me - Lucifer asks Sam to say Yes, and Sam says No. Lucifer assures him that eventually he will say Yes but promises that he won't force him to do it.
- The End - In an alternate timeline, in 2014, Sam assents to Lucifer in Detroit; Zachariah again tries to convince Dean to say Yes to Michael, and again Dean refuses.
- Changing Channels - Gabriel commands them to say Yes; they both refuse.
- Abandon All Hope...- After Dean fails to kill Lucifer with The Colt, Lucifer tells Sam that he has forseen Sam saying Yes and that it will happen within six months.
- The Song Remains the Same - Michael himself speaks with Dean and insists that it is his destiny to say Yes after having gotten John Winchester to say Yes by promising to save his wife.
- Dark Side of the Moon - Zachariah is angry with Sam and Dean for their continued refusal; he plans to beat them up regardless of whether or not they say Yes.
- 99 Problems - Sam starts to worry that Dean will say Yes to Michael.
- Point of No Return - Dean almost says Yes to Michael, but Castiel, Sam, and Bobby stop him. Under coercion from Zachariah, Dean finally says Yes to Michael, but changes his mind, kills Zachariah and escapes with Sam, though Adam is left behind and is later revealed to have been taken by Michael as his vessel, having earlier agreed.
- Two Minutes to Midnight - Sam decides to say Yes to Lucifer as part of the plan to re-imprison him in the Cage.
- Swan Song - Sam says Yes to Lucifer. Lucifer, despite knowing Sam's true intentions, possesses him.
- I Think I'm Gonna Like It Here- Hael planned to possess the now-human Castiel in order to become stronger and tried to threaten him into saying Yes after being badly injured, but Castiel killed her instead. In order to save Sam, "Ezekiel" takes on Dean's form and converses with Sam in his mind, convincing him to say yes to "Dean's" plan to save him which proves to be enough to allow Ezekiel to possess him and heal him from within.
- I'm No Angel - Bartholomew is using an internet preacher to get devout people to say "Yes" when angels come asking them to be their vessels. A young woman comes to Bartholomew and offers herself up, but proves to be an unsuitable vessel and explodes.
- Heaven Can't Wait - A young man says Yes to Ephraim who proceeds to go on a rampage, killing everyone he can find who feels any sort of emotional pain before being stopped by Dean and Castiel.
- Holy Terror - Bartholomew has started having the preacher, Buddy Boyle, target smaller groups for possession in order to ensure his own followers get vessels and not everyone else. Malachi and his faction do the same using a choir woman possessed by one of his followers to target a group of college students, but the students are killed by angels working for Bartholomew before they can be possessed.
- Road Trip - Sam revokes his permission to Gadreel, expelling the angel who is forced to return to his original vessel who once more says Yes.
- The Devil in the Details - Lucifer tries to get Sam to say Yes again by taking him through his memories, then resorting to violence when Sam still refused. After Dean and Castiel arrived to stall Lucifer until Rowena can banish him, Lucifer possesses Castiel after he consents, nullifying Rowena's spell and escaping the cage again.