Billie and her brother Austin came to Salem in late 1992, adding a new dynamic that had a ripple effect upon the populace. Within months, Billie lost a job due to her drug habit, became Carrie Brady's roommate, and nearly fell back into prostitution. The intervention of Carrie's Uncle Bo saved her. Then, when an old crime pal came through town, his stashed money drew Billie into Jack Deveraux's shenanigans.

Billie Reed came to Salem shortly after her brother Austin arrived in 1992. A product of a dysfunctional household, Billie grew up with her share of problems; she was a porn star and stripper who was sexually abused by her father. In Salem, she lost her first job due to her drug habits and would have fallen back into prostitution if it weren't for the saving graces of Bo Brady. She moved in with Carrie Brady and began to pull her life back together.

Billie and Austin were both shocked when their presumed-dead father, Curtis, resurfaced in Salem. Shortly after his arrival, Curtis was found shot to death with Billie's gun. Although innocent, all fingers pointed to Billie and she was charged with his murder. Throughout the entire trial, Bo stood by her side. By the end of the ordeal, it was revealed that Stefano had killed Curtis in self-defense and that Kate Roberts was Billie's biological mother. Later, Bo proposed to Billie and she happily accepted.

Meanwhile, Gina showed up in Salem to complicate matters. Gina didn't regain her full memory as Hope until after Bo and Billie were married but that didn't stop her from coming between the newlyweds. Hope's presence was too much for Bo; his marriage to Billie was soon declared invalid. She left for Paris to promote her Countess Wilhemina cosmetic company but returned to Salem in time to prevent Bo from remarrying Hope. Billie and Bo went undercover to expose an illegal drug ring and rekindled their love in the process. They were forced to marry in Rome in order to make their cover convincing and their bond grew even deeper. Later, they conceived a child named Georgia but Billie miscarried during her pregnancy and was devastated by the loss, but Billie did use it to her advantage and blamed Hope, which everyone later discovered wasn't true.

Bo and Hope eventually reconciled and Billie resumed her secret, and codependent, relationship with Bo's brother, Roman Brady. She continued to have feelings for Bo and slowly rebuilt her friendship with Hope.

Billie was involved in fierce competition with her mother over Nicholas Alamain. Despite her best efforts to win him over, Nick was hopelessly in love with her mother. Feeling betrayed and defeated, Billie contemplated exposing the affair to Victor but ultimately took the high road and decided against it. Billie left Salem for a much needed break from her mother and relationships.

Upon her return in 2002, Billie's car was hit by a falling meteor. She pretended to not know who she was and, with the help of her little brother Philip, escaped from the hospital. She lived with Kate while attending the Salem police academy, but after being shot while working with Larry Welch (whom she believed to be part of the ISA), Billie left town again, heading to London to join the ISA at Roman Brady's suggestion. She wasn't heard from for months, but then she had a message for Bo...she knew who the Salem Stalker was, but she would only tell him. Unfortunately, she went missing at the same time.

Billie turned up on Melaswen, and was instrumental in helping the Salem residents to escape the island. She was one of the lucky ones who made it back to Salem, where she soon admitted that she never had and never would stop loving Bo Brady. She was preparing to leave town when Bo broke the news to her that there was information found on the disks they managed to smuggle out that indicated their daughter Georgia was still alive, even though everyone believed she was stillborn in the bayou years earlier. Billie and Bo began searching for their daughter, who would now be sixteen. After searching the DiMera castle in Europe, they finally learned that Georgia had been adopted as a child, and lived right in Salem.

Unfortunately, the search for Georgia stagnated, and Billie needed a new cause to focus her attention on. When Abby's friend Chelsea was in a serious car accident and her parents died, Billie took the teen in after learning that her family had been virtually penniless. The two of them moved in with Patrick Lockhart. It wasn't long before they learned that Chelsea was, in fact, Billie's daughter -- but Chelsea couldn't stand her. Billie tried with her daughter, though, and they were finally able to formulate a relationship and even became quite close. After a brief relationship with Steve Johnson, which ended when he had full recollection of his past with Kayla, a depressed Billie ended up getting drunk one night and fell into bed with Chelsea's friend Nick, who had come to see her to get advice about Chelsea. Chelsea was devastated to learn that her mother had slept with Nick and it took some time to forgive them.

Billie later got a job at Salem University, heading up the campus security division. While there, a number of Chelsea's sorority sisters were raped. Billie helped the girls figure out that Ford Decker was responsible for the rapes. When Ford accidentally died at the sorority house, Billie helped the girls come forward with the information. None of the girls were punished, but unfortunately Billie lost her job. However, Victor offered her a job heading up the securities division of the Titan offices in London. Billie packed up and left Salem to take the job.

In April of 2009, while still in London, Billie was in a terrible accident. Although she recovered, she required intensive physical therapy and multiple surgeries. Chelsea moved to London to help her mom through the recovery.

In March of 2012, a fully recovered Billie came to Salem, seemingly to help her mom run Countess Wilhemina Cosmetics. However, it was soon revealed that Billie was back working for the ISA and was assigned to get information on Stefano. Billie convinced her mom to let her move into the DiMera Mansion.

But, Stefano was actually working as a CIA informant, so her investigation came to a halt. And, when Stefano and Kate's relationship fell apart, Billie stayed in town to support her mom and work with her at Mad World Cosmetics. But Billie and Kate eventually grew apart. Frustrated with Kate's scheming, Billie decided to take a new job in Europe. But, she made peace with Kate before she left.