The 66 Seals

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Dean: Why break the seal anyway?

Castiel: You think of the seals as locks on a door.
Dean: Okay, last one opens, and?

Castiel: Lucifer walks free.

– , 4.02 Are You There, God? It's Me, Dean Winchester

Lucifer cannot rise. He does and Hell rises with him.

Castiel, 4.07 It's The Great Pumpkin, Sam Winchester

4.02 Are You There, God? It's Me, Dean Winchester

In this episode Lilith casts a spell to bring about the Rise of the Witnesses - people whom hunters failed to save. While Sam, Dean and Bobby stop the Witnesses, the seal is broken.

Castiel reveals that the 66 Seals are the key to unleashing the Apocalypse. Lilith is breaking them one by one. Even if the evil thing unleashed is quelled or defeated, the seal is not restored and Hell on earth for all creation is one step closer.

4.07 It's The Great Pumpkin, Sam Winchester

The Raising of Samhain breaks another seal.

4.09 I Know What You Did Last Summer

It is revealed by Anna Milton that whilst 66 Seals need to be broken for Lilith's plan to succeed, there are around 600 possible Seals. No-one knows which ones she will break, making it near impossible for anyone, even the angels, to predict her movements in accomplishing this task.

4.12 Criss Angel Is A Douchebag

Ruby informs Sam that 34 of the 66 seals have been broken. She says the angels are losing, and urges him to kill Lilith.

4.15 Death Takes A Holiday

Alistair is trying to break a seal that requires the death of two reapers on the night of the solstice. Castiel, pretending to be Bobby Singer tells Sam of this, informing Sam how it is described in a "version of Revelations":

And he bloodied death under the newborn sky
Sweet to taste
But bitter once devoured

Castiel needs Sam and Dean as the demons are holed up in a refuge protected by sigils that keep angels out. The boys are successful in stopping the seal being broken.

4.16 On The Head Of A Pin

As Dean is torturing Alastair, he reveals that dean was responsible for the first seal breaking:

Alastair: And it is written that the first seal shall be broken when a righteous man sheds blood in hell. As he breaks, so shall it break. We had to break the first seal before any others, only way to get the dominoes to fall, right? Top of the one at the front of the line. When we win, when we bring on the Apocalypse and burn this earth down, we owe it all to you, Dean Winchester.

He reveals that it had been hoped that John Winchester would be that man, but he didn't break.

Castiel confirms to Dean that he was indeed responsible for the first seal being broken, even though Heaven "laid siege" to Hell to try and rescue him. He tells Dean they raised him from Hell, because only the righteous man who broke the first seal can stop the rising of Lucifer and the Apocalypse - although he is unclear on the details.

4.21 When The Levee Breaks

Rufus calls Bobby with news of more of the The 66 Seals being broken. The seals Rufus Turner reports being broken are : ten species extinct in Key West, fishing crew of fifteen goes blind in Alasaka, and a teacher on New York kills 66 students, all in one day.

Castiel asks for Dean's fealty, and says he can stop the Apocalypse.

Ruby tells Sam there are only two or three seals left to be broken. She says only "Lucifer's first" can break the final seal - and that is Lilith. This renews Sam's desire to kill Lilith.

4.22 Lucifer Rising

Lilith's death is final seal, the one which will free Lucifer. "And as it is writen, the first demon will be the last seal." This has been known both by the angels - who want the apocalypse to come, and by the Lilith and Ruby, who has been helping manipulate Sam to get him to kill her. Castiel finally reveals the fact of the final seal to Dean, but he arrives to late to stop Sam killing her and freeing Lucifer.