Castiel: Will you look at her? My caretaker. All of that thorny pain, so beautiful.
Meg: We've been over this. I don't like poetry. Put up or shut up.
As an angel and a demon, Castiel and Meg are sworn enemies on opposites of the battle for the Apocalypse. Their first meeting, though full of sexual banter, is resolved by Castiel pushing Meg into a line of holy fire. However, over the course of the series, the two rely on one another and work together on the same side, both with and without the Winchesters. Their trust and camaraderie in later episodes is unmistakable, and a shared kiss in their second episode together cemented the foundation for this popular pairing.
Castiel and Meg meet face-to-face for the first time after he is trapped in the ring of holy fire by Lucifer, who asks Meg to watch him. With Castiel trapped, Meg proceeds to taunt him about how they are winning. Castiel plants seeds of doubt in her mind when he points out to her that Lucifer doesn't care about demons, which seemed to upset Meg greatly. As she steps forward to argue, Castiel telekenetically moves a pipe down onto Meg which knocks her through the ring of holy fire and into his arms. He then attempts to smite her but it doesn't work, causing Meg laugh at him. She taunts him about how he can't kill demons being far from Heaven, and asks him what he plans to do now. Castiel replies by throwing her onto the fire, and as she screams in agony he walks over her body to escape from captivity.
Forced by Sam to work with Meg, Castiel agrees to work with her in order to find Crowley and retrieve Sam's soul. When the group is ambushed by hellhounds, Meg stays behind to fight them off. In need of a weapon, she kisses Castiel in order to steal his angel blade. As she pulls away, Castiel pushes her against the wall and kisses her again. Meg is stunned, and Castiel says that he learned that from the pizza man -- who is a character on a pornography film he found and watched earlier "because it was there." The rest of the gang leaves, and Meg faces off with the hellhounds. After the mission is finished, Dean teases Castiel, asking if he wants more time with Meg, but Castiel says no and is confused as why he would want to spend more time with Meg.
Meg and Castiel meet again, but Castiel is suffering from amnesia and goes by the name Emmanuel Allan. When Castiel regains his memory, he transfers Sam's sickness to himself, which leaves him in a comatose state and necessitates his stay at the mental hospital. Meg poses as a nurse there and stays to watch over him, stating that she was loyal to Lucifer, not Crowley, and will therefore protect Castiel in order to screw with the King of Hell.
I know what I'm supposed to do. And it isn't screw with Sam and Dean or lose the only angel who'd go to bat for me.
Meg is seen reading a magazine at Castiel's bedside when he finally awakens. He exhibits strange behavior, including his fondness of bees and his adamant refusal to participate in any violence. He also grows attached to Meg, talks about her "thorny beauty", and asks her if she's okay. An angel, Hester, attempts to kill Castiel, but he is saved when Meg returns and kills Hester.
Meg is fed up when Castiel forces her to bring him to the Winchesters. When Crowley shows up and threatens Meg, Castiel defends her. Crowley leaves her alone for awhile because, as he points out, the Winchesters need Castiel to defeat Dick Roman, and because Castiel is fond of Meg and would be upset if she was taken away. When Dean yells at Castiel, causing him to leave for a short time, Meg chides him for his actions and reminds him that Castiel has the unique ability to tell the Leviathans apart, a crucial skill since Dick Roman had made several duplicates of himself to throw off Dean and Sam. Meg also stays to help the Winchesters and Castiel in their plan to take down Dick Roman by acting as a distraction for the Leviathans outside SucroCorp.
Go. Save your brother... and my unicorn.
Castiel rescues Meg from Crowley's demons, and he bandages her wounds. While doing so, she flirts with him about the time they kissed in 6.10 Caged Heat. Meg tells him, "When all this is over, I'm going to order some pizza and we're going to move some furniture around." Castiel listens intently and eventually gets her meaning and accepts her offer. When asked, he says that he remembers their kiss, and he considers it a good memory. In the next room, Sam and Dean wonder if they should trust Meg and Castiel, referring to them as "Megstiel."
While discussing Sam's year of leaving hunting for someone he loved, Meg understood how the right person could change someone, implying deeper feelings for Castiel. When telling Sam to go after Dean and Castiel, she refers to Castiel as "my unicorn" which is what she had called Amelia Richardson after learning that Sam had stopped being a hunter because of her. Meg ultimately sacrifices herself to hold Crowley off to buy Sam, Dean, and Castiel the time they need to get away. With her last words, Meg taunts Crowley about Castiel getting away with the angel tablet.
While in hiding from the angels, Castiel uses the alias "Clarence" which was Meg's nickname for him. This implies that Castiel still holds some affection for Meg.