While prayer is used by those of religious faith, it is also used as a means of communication between humans, angels, and God. Nephilim can also receive prayer. Long before they knew of the existence of angels, Sam prayed every day.
- "Well, I feel stupid doing this. But... I am fresh out of options. So please. I need some help. I'm praying, okay? Come on. Please."
Looking to give himself to Michael as a vessel, Dean finds a preacher on the street and asks him to pray to the angels. Castiel hears this prayer and arrives, beating Dean in anger before taking him back to Bobby's.
- "Well, let's give it a shot. Now I lay me down to sleep. I pray to Castiel to get his feathery ass down here."
After he gets no answer, he tries once more:
- "Cas! Don't be a dick. We got ourselves a... plague-like situation down here, and... do you...do you copy?"
In an effort to get Castiel's attention, Sam uses the plot to Raiders of the Lost Ark to get Castiel to meet him. When Castiel refuses to talk, Sam threatens to hunt him down and kill him, before pleading that he needs Castiel's help.
- "Castiel, we need you. It’s important. Cas, we found something. It’s this gold box. Apparently Nazis were after it back in the day, someone opened it and their face melted off. I think it’s – ready for this – the Ark of the Covenant. Yeah. So…"
- "Castiel. The, uh, fate of the world is in the balance. So, come on down here. Come on, Cas, 'I Dream of Jeannie' your ass down here pronto. Please."
- "Castiel, it's Sam. Um, so look, I don't know if you're in on this whole Ben-Lisa thing, but if you have any heart whatsoever, bring 'em back to us, man. C'mon. Please. I'm begging you. I am begging you, do you understand?"
- "Hey, Castiel. Um... Maybe this is pointless. Look... I don't know if any part of you even cares, but, um, I still think you're one of us, deep down. I mean, way, way, way off the reservation, but... Look, we still have till dawn to stop this. Let us help. Please."
Some time after Sam completes the first of the trials to close the Gates of Hell, Dean prays to Castiel to watch over Sam.
- "Cas, you got your ears on? Listen, you know I am not one for praying, 'cause in my book it's... it's the same as begging. But this is about Sam, so I need you to hear me. We are going into this deal blind... and I don't know what's ahead or what it's gonna bring for Sam. Now, he's covering pretty good, but I know that he is hurting, and this one was supposed to be on me. So, for all that we've been through, I'm asking you... you keep a lookout for my little brother, okay? Where the hell are you, man?
In order to purify his blood for the demon cure ritual, Sam confesses his sins in a private prayer.
- "Cas, are you there? Sammy's hurt. He's hurt, uh – he's hurt pretty bad. And, um... I know you think that I'm pissed at you, okay? But I don't care that the angels fell. So whatever you did or didn't do, it doesn't matter, okay? We'll work it out. Please, man, I need you here... Screw it. Okay, listen up. This one goes out to any angel with their ears on. This is Dean Winchester... And I need your help. The deal is this – Linwood Memorial Hospital... Randolph, New York. The first one who can help me gets my help in return... and you know that ain't nothin'. Hell, it's no secret that we haven't always seen eye to eye. But you know that I am good for my word. And, uh, I wouldn't be asking if I wasn't needing, so..."
The now-human Castiel overhears a woman praying in a church for the angels to heal her husband Mike. Castiel asks what she would do if she knew that no one was listening and God has left. She tells him that his lack of faith doesn't cancel out hers, and that someone is listening.
- "Okay. I'm... unfamiliar with this end of the process. Of course, no one may be listening, um, but I – I do need assistance. I have questions, and there seem to be no answers. I... I wouldn't presume to ask for help if I weren't desperate, but I need help. I'm lost. I need your guidance. I don't know how humans do it."
Castiel tells Claire Novak that angels are able to find those who pray to them. When Claire tells him she gave up praying a long time ago, he reveals that the prayer does not have to be formal, and that he could pick up on a "longing" coming from Claire.
- "So... I know it's been a long time, but... Dean and I, we've -- we've been through a lot of bad. But this is different. This is my fault, and I don't know how to fix it. And if I have to die, I've made my peace with that, but... Please. Dean deserves better. Dean deserves a life. There are people out there, good people, who are going to suffer because of me, and I am not asking you to clean up my mess. Hell, I don't even know if you're out there, but... If you are... And if you can hear me, I, um... We need your help, God. We need to know there's hope. We need a sign."
Sam is in his room at the Bunker kneeling in front of his bed with his back to his open door, praying to God.
- "So, uh... on the off chance that you're actually listening, uh... Uh, I gotta be real honest. The visions aren't making a whole lot of sense to me. Truth is... I don't know what's what. Please. What are you trying to say?"
When Dean sees this, he begins to admonish Sam, telling him he should not count on God to help them due to his past indifference with the Apocalypse.
- "Okay, Chuck… or God, or whatever. I need your help. See, you– you left us. You left us. You went off. You said… You said the earth would be fine because it had me… and it had Sam, but it’s not, and we’re not. We’ve lost everything. And now you’re gonna bring him back. Okay? You’re gonna bring back Cas, you’re gonna bring back Mom, you’re gonna bring ‘em all back. All of ‘em. Even Crowley. ’Cause after everything that you’ve done, you owe us, you son of a bitch. So you get your ass down here and you make this right, right here and right now. Please. Please help us."
As a shootout rages in the warehouse, Father Lucca Camilleri says a prayer for Sam and Dean.
In an attempt to be "God" in earnest, Lucifer sits on his throne and begins listening to the prayers of humanity. He quickly becomes annoyed by the sheer volume of the prayers, but his interest is piqued when he hones in on two priests performing an exorcism and decides to aid them in sending the demon, Anthony, back to Hell.
- "Jack, Jack. Jack, I don't know where you are, and I don't even know if you can hear this prayer, but we need you. We need you."
After finding out what happened to his family, and killing Frank Kellogg, Nick gets drunk and begins praying to Lucifer for help in removing his pain. His bond as his former vessel somehow awakens Lucifer in the Empty.
- "All right... I'm not very good at this, but the priest said it would help, so, um... I'm gonna try. I say that I do the terrible things I do because I couldn't find who killed Sarah and Teddy. And that once I did, I'd be free of this darkness and this rage... but I lied. Truth is... I like doing these things, and I don't want to stop. I'm bonded to you and what you are. I mean, it's -- it's -- It's how you first found me. I don't know who I am if I'm not you. No consequences. No pain. No sorrow. I want that back. I want it back. I don't want to feel now what I didn't feel then. Where are you? Where are you? Help me. Help me."
As Castiel fights the Cosmic Entity, Dean prays to him to resurrect Jack so Lily Sunder can complete her spell and save him. Castiel hears the prayer and makes a deal with the Entity to exchange himself for Jack.
- "Cas, I hope you can hear me. We've got Jack. His shell -- it's ready to go. Here's hoping that you're staring at him right now. So, if you are, then, uh, do your thing, okay? Amen."
With the Winchester family reunited and sitting down to have their first family dinner, John says a quick thankful prayer to whatever brought them all together, followed by each family member punctuating it with their own "Amen."
- "All right. Near as I can tell, we have two choices. All right, we can think about what's coming. Or we can be grateful for this time that we have together. Now, me I choose grateful. So, to whatever brought us together, we owe you one. Amen."