Born Harleen Quinzel, Harley's mother is somewhat harsh , but she is also a forgiving lady, who constantly calls Harley evil and compares her to other heroes. Harley's younger brother is a dead beat with children from at least two different women and, he still lives in his mothers house. Harley apparently sent him several large sums of money to get his life on track, but he squandered it. Harley's father is a criminal con-man, known for squandering women of their money with his charm. Harley states that the main reason she became a psychiatrist was so she could understand why her father did what he did to their family.

Harley’s origin was adapted from the Batman: The Animated Series episode and comic entitled Mad Love. The story starts off with Dr Harleen Quinzel working as an intern in Arkham Asylum. She discovered the Joker and quickly became fascinated with his insane motives. She voluntarily asked for a chance to analyze him. During one of their sessions the Joker tells her about his tragic past and how his father abused him. She gained sympathy for him and quickly fell in love with him. She helped the Joker escape dressed up a the Harley Quinn. So, started her career as the Joker's sidekick.

Later, Harley finds out that everything the Joker had told her was most likely a lie or scam. He was deliberately telling her what she wanted to hear to endear himself to her. This is something that Joker does to Harley all throughout their relationship. She knows this and continually tries to leave him but like an abused spouse, she just keeps going back to him. Of course Harley gets her license revoked when her superior Joan Leland finds out she is the one who released the Joker.

Eventually Harley got caught by Batman and she is put in a cell at Arkham - she is able to escape time and time again. One time she was able to escape Arkham when an earthquake hit, and she soon rejoined up with the Joker and helped him in his crimes. Later, in another retelling of her origin it is explained that she was a psychology student working part time as a stripper to pay her bills. Ever since the beginning of her relationship with the Joker, Harley has played a very submissive role. She has often been used and abused by the Joker to the point where her life has been threatened on several occasions. Yet she remains faithful to her man and stands by him when things go wrong. Their relationship is quite strange, as the Joker rarely shows any affection towards her.