In the 2000–2001 season, Abby is visited by her mother, Maggie (played by Sally Field), who suffers from bipolar disorder. Abby's childhood is revealed to have been very difficult. During her childhood, she was forced to cope with her mother's erratic behavior when she was not taking her medicine. She also had to deal with her mother's long absences, and had to take care of her younger brother Eric (played by Tom Everett Scott).
The audience later meets Eric, who has been in the Air Force but went AWOL. He, too, is showing signs of bipolar disorder, but refuses to accept this.
Abby's father, Eddie, left the family when Abby was a child, due at least in part to Maggie's uncontrollable behavior. Abby reunited with her father (Fred Ward) in season 13, when he initially approached her under the disguise of being a patient named Eddie Jackson before finally revealing his true identity to her.
Throughout her stay at County General, Abby has been generally friendly and well-liked by most of the staff. She is considered open to talking and listening, yet she remains humble and cautious about her personal life. She has befriended many colleagues in the ER who have come and gone, particularly the female co-workers including Carol Hathaway and Susan Lewis, and later Elizabeth Corday and Kerry Weaver. She is now close friends with Dr. Neela Rasgostra. Currently she and Luka Kovač are the longest residing doctors in the County ER and have become the senior figures on the show.
Abby's next relationship is with Dr. John Carter. Abby discovers Carter shooting up on painkillers. She tells the attending doctors about it, and at their urging and with their help, Carter enters a rehabilitation program. Once he returns, he sees Abby at an AA meeting. She tells him that she is a recovering alcoholic and had been sober for five years. She agrees to become his AA sponsor. Abby and Carter develop a very strong friendship. This strains her relationship with Luka.
Several months later, Abby has a particularly horrible birthday and starts drinking again. When Carter catches her having a beer, he confronts her, and she tells him not to worry about her. When Dr. Mark Greene passes away, Carter seeks solace in Abby. She returns to her AA meetings, telling Carter she did it for him, and they become a couple. Abby continues drinking, and Carter compulsively tries to "fix" her. At one point, Carter is ready to propose to Abby at a special dinner he's arranged for her, but at the last minute, he ends up putting the ring back in his pocket and though they discuss it briefly in a later episode, he never tries again.
Their relationship is badly strained when Carter's grandmother (portrayed by Frances Sternhagen) dies, and Abby's brother, Eric, conclusively diagnosed with bipolar disorder, attends the funeral with them and falls into her grave. Soon after that, Carter flies to the Congo and joins Luka, who is volunteering with Doctors Without Borders. When Carter goes to Africa for the second time (presumably to recover the body of Luka, who, in a plot twist, has not actually died), he sends Abby a break-up letter, and their relationship finally ends. Just as with the end of Luka and Abby's relationship, Abby and Carter remain close friends after a period of distance between them.
Abby briefly dates a medical student named Jake for a while in season 11, but their relationship eventually fizzles when Abby does not respond positively to Jake's desires to stay in Chicago to be with her. She also begins to grow close to Susan Lewis and Kerry Weaver.
In Season 12, Abby rekindles her relationship with Luka in the episode "The Human Shield." Initially, they decide to remain friends, but soon become lovers. Three weeks into their relationship it is revealed that Abby is pregnant. She and Luka decide to keep the baby. Luka proposes to Abby while she is pregnant, but Abby is not comfortable with the idea and was discouraged because of her past problems, and later claims she 'doesn't need a white dress' to prove she loves him. Their baby, a son called Joseph or Joe (after Luka's father, Joe), with Joe for short (after Joe Frazier, the boxer whom Abby's long-disappeared father was a fan of) is born by emergency C-section at the beginning of season 13. Abby also has to have an emergency hysterectomy. He is premature and spends several weeks in the hospital's NICU, requiring surgery during his stay. Abby and Luka's relationship becomes strained during this period, but appear much happier in later episodes, caring for their now healthy baby boy.
Throughout Season 13, Abby is shown growing into her role as Joe's mother, first by taking time off to be with her seriously ill baby, then by participating in classic maternal activities like Mommy and Baby classes and walks in the park, and then later by gradually reintroducing herself into the ER world. Mid-season tension develops between Abby and Luka, partly as the result of Luka's apparently paranoid behavior regarding Curtis Ames, a disgruntled former patient who has sued Luka due to a stroke he suffered that cost him the use of his arm. Ames eventually breaks into Abby and Luka's apartment, and demands to see Luka. Abby tries to bargain with him, telling him that she used to be an alcoholic, and recounting an occasion where she felt as if she had hit 'rock bottom'. Luka is taken hostage, threatened and has his hand crushed by Ames, but survives his ordeal when Ames commits suicide. In the next episode, an emotional Abby asks Luka to propose to her again. She says if they got through the shooting incident and the Curtis Ames nightmare, they can get through anything - he proposes and the couple get engaged. Later Luka realises that Abby is hesitant and being 'freaked out' by planning the wedding, so he decides to prepare a surprise wedding for her. At first, she has her doubts and fears but eventually she agrees and asks one of her best friends, Neela Rasgotra to be her maid of honor.
At the end of the thirteenth season, Abby and Luka plan to honeymoon in Hawaii. However, the night before they are due to depart, Luka receives a phone call from Croatia informing him that his father is ill, so the honeymoon is put on hold until Luka can return from his urgent trip abroad. After Luka's departure, Abby along with the ER staff has a tough time with the stern and poised new ER Chief Kevin Moretti, who plans to mold the department into a more efficient and professional work environment, but Moretti quickly tells Abby he is very impressed with her work. In Season 14, Abby is struggling to deal with Luka's absence, raise Joe and work at the ER; in "Gravity", Joe is injured after falling off a jungle gym at the playground and Abby ends up falling back into drinking at the episode's end. Her drinking problem continues to escalate, and Abby realizes how bad it is in "Blackout" when she shows up drunk to a "party" in honor of Pratt and Morris passing their boards. Abby finds herself waking up at 3am in Moretti's apartment, realizing later (after sobering up at the airport when trying to find a flight to Croatia to see Luka) she slept with him. When Luka arrives back to Chicago, he soon gets news that his father has died. Abby tells Luka to take Joe to Croatia for the funeral while she seeks help for her alcoholism. Upon her return to the ER, Abby faces the true reality of her situation; she must tell her co-workers the truth about her disease. The only negative reaction at work is from Sam, played by Linda Cardellini, who diplays disgust at Abby's weakness, but the two women mend fences when Sam tells Abby she was being harsh because of her own long history of being around alcoholics who refused to clean up their lives. Luka is angry that she cheated on him and put their son's life in danger, and decides to move out of the apartment.
Abby and Luka embrace at the end of the 14th season. Abby tells Luka how much she loves him and they kiss. At the conclusion of the 14th season, it would appear that Abby and Luka are willing to continue to work on their marriage.
In "21 Guns," the 12th season finale, a shootout occurs in the ER between the police and several prisoners who are trying to escape custody. Abby immediately drops to the floor next to the admit desk, which is the center of the shootout, and apparently suffers a couple of minor cuts due to the glass shards. While rolling on the floor to get away from the glass, her stomach slams into a metal cart that has overturned in the small space. She leaps up and begins to tend to the more seriously injured Jerry, the admission worker. In the last scenes, it is revealed that her injuries are serious, and her pregnancy is affected. She notices blood on the bottom of her jeans and faints. She leaves a hand print of blood on the window as Luka watches helplessly in the next room. He had been incapacitated and tied to the gurney by the prisoners, who had injected him with vecuronium, a drug that was intended for a patient. He had to be intubated as the drug had seriously relaxed most of his body muscles, and he stopped breathing and would have died if Sam had not defied her captors and treated Luka so he didn't choke to death. Kerry Weaver finds both Abby and Luka and gets their treatments started right away.
Towards the end of season 14, Abby applies for an attending position at County General. But under the advice of Pratt, she applies at other medical facilities and, in the penultimate episode of the season, Tandem Repeats, accepts a job at a new, state-of-the-art hospital - only to decline the offer several hours later when she is offered the attending spot at County after all.