When Connor Macleod sees his old friend Rachel die in an explosion, he's had it with his immortal life and the endless pain it brings him and those he loves. He locks himself inside the Sanctuary, a Watcher-organized retreat stationed on holy ground, where immortals who are tired of the game can go to forever escape it, as well as to ensure that The Prize never falls into the wrong hands. But when an old enemy, Jacob Kell, and his posse of assassins attack the Sanctuary and kill everyone there but Connor, he is forced out into the open and into battle. Kell and Connor were friends once, and knew each other back when Connor was cast from Glenfinnan; he returned when news came that his mother was to be burned at the stake, and in the attempt to free her, Kell was killed by none other than Connor himself, and became an immortal, bitter with hate, and devoted to making Connor's life a living hell...

There exists an ancient manuscript still writing itself called the Lexicon. It supposedly tells of the coming of the Anti-Christ, and happens to fall into the hands of an unsuspecting woman. Now, she is being pursued by angels intent on obtaining the information from the book.

In Bucharest, Allison is protecting the mysterious bible, "The Prophet Lexicon", where the last chapter about the apocalypse, called Revelations, discloses the name of the Antichrist in its last page. Meanwhile, the evil and jealous leader of the renegade angels Thrones, Stark, forces the hit-man Dylan to kill Allison to get the information about the Antichrist, but Dylan mysteriously feels attracted by the woman, protecting her against the Thrones. Allison seeks John Reigart for help, but Satan tell her that he is interested in the apocalypse to gather millions of souls to Hell. Alone and betrayed, Allison discloses the truth about her origins, while protecting the Lexicon.

Gabriel returns to Earth to prevent the birth of a child conceived by one of his kind (the Angel Daniel) and one of God's "monkeys" (a human woman - Valerie). The coming of this child has been prophecised by a monk, Thomas. When the Angel Daniel kills members of Gabriel's army of angels, Gabriel instead employs the assistance of a teenage girl (Izzy) who has just committed suicide. Gabriel keeps her alive to assist him in his war against Daniel and the other angels which climaxes in a battle in Eden.