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Knox first appears in Home, the final episode of Season Four of Angel, when he gives Fred a tour of Wolfram and Hart's science lab. In Season Five, Fred becomes Knox's boss, although the two seem to work mostly as partners, and Knox quickly develops a crush on her. Fred rejects Knox's advances at first, but the two date for a while, sharing a drink after the office Halloween party. Fred eventually decides that they had best remain friends and co-workers, and pursues a relationship with Wesley.
In "A Hole in the World", Knox is revealed to be a worshiper of Illyria, one of the Old Ones, and the mastermind behind the demon's resurrection in Fred's body. Once Illyria has taken over Fred's body and returned to Wolfram & Hart to recuperate her full powers, Knox reveals himself as her Qwa'ha Xahn, her High Priest. Knox has worshiped Illyria since he was eleven and confesses to spending hours staring at illustrations that represent the demon. Illyria takes Knox to her former site of worship, hoping to break the lock on the portal to her temple. Before she can jump through the portal, she and Knox are confronted by Angel, Spike and Wesley. In his grief for Fred, and rage at Knox's betrayal, Wesley shoots Knox dead. Ironically, Wesley only does so after Angel makes a heroic speech about the sanctity of all human life, even Knox's, and how their willingness to save Knox despite what he had done to them was what made them better than demons. As Knox falls to the ground, dead, Angel turns to Wesley and, slightly annoyed, asks, "Were you even listening?"