Jamie Moriarty is Sherlock Holmes' nemesis. After Sherlock interrupted several of her plans when he worked for Scotland Yard, she tricked Sherlock into falling in love with her so she could study him, knowing her only as Irene Adler.
When Sherlock Holmes interrupted several of her plans of assassinations in London, she seduced him into falling in love with her as so she could study him, finding him curious. When she discovered that Sherlock was no threat at all, she staged Irene's death, and resumed her business as Moriarty.
After she staged her death, Sherlock got addicted to drugs, moved to New York, and eventually checked-in to rehab and got on the road to recovery. When she heard about Sherlock's recovery, she followed after him to New York to see how far he'd recovered. She eventually contacts Sherlock as Moriarty, disguising herself behind a man's voice. She leads him to a house in Queens, where he find her as Irene, alive. Appearing as if she has been held captive, she is checked-into a hospital, and eventually moves in with Sherlock under his care. When someone breaks into his house and leaves a flower at her bed, Sherlock takes her to a safe house and plans to elope with her. After Sherlock sees her naked back and sees one of her moles missing, he figures out that she has been faking her own death and reappearance, and suspects her of working for Moriarty. Later, when one of her assassins attacks Sherlock, she comes to the rescue, and reveals herself to be Moriarty and how she tricked him back in London. She tells him to let her win, or she will hurt him. She later visits Sherlock in the hospital when he supposedly overdosed on drugs, wanting to help him. Sherlock records their conversation without her knowing, and gets her on tape admitting to ordering a murder.