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Harley is set to begin her new life, but she needs a job first! Enter the Coney Island Roller Derby! It’s game time as Harley sets out to destroy her competition—literally! Dr. Harleen Frances Quinzel is depicted as having been a psychiatrist at Gotham City's Arkham Asylum. Gotham City Sirens shows Harley visiting her family for the holiday season, in which they are portrayed as being very dysfunctional. It is stated the reason Harley pursued psychiatry was to understand her own broken family.

The character's origin story relates that Harleen Quinzel was once a psychiatrist at Arkham Asylum and was assigned to treat the Joker. She eventually falls in love with the Joker and becomes his lover and accomplice after warping her mind through a series of lies. She follows suit in the Joker's clown-themed, criminal antics and adopts the name Harley Quinn, a play on "Harlequin" from the character in commedia dell'arte. Speaking with a pronounced Northeastern accent, Harley refers to the Joker as Mistah J and Puddin', terms of endearment that have since been used in nearly every adaptation in which the two characters appear.