Sam is a nurse and single mother; she has a son, Alex (played first by Oliver Davis, later by Dominic Janes). Alex was born when she was fifteen; she has had to raise him mostly on her own. She comes from a family of losers and alcoholics; her anger towards Abby Lockhart in Season 14 when Abby tells the staff she had a relapse while working is explained when she tells Abby that she came from a long line of drunks who never tried to stop drinking.
Viewers first meet Sam in the Season 10 episode "Out of Africa," where she distinguishes herself by quickly and effectively giving an intravenous sedative to an unruly patient. Sam shows herself to be an assertive, experienced, and talented nurse throughout the episode, though she loses her professionalism a bit when she discovers Dr. Luka Kovac's unknowing part in her son Alex's diabetic fit while he befriends the boy. She replaces Abby Lockhart who was head nurse, but decided to become a doctor instead. She stands out early on: in the episode "Impulse Control", she punches an assault victim's abusive boyfriend in the face when he threatens her as she tries to call the police, but overcomes Kerry Weaver's knee-jerk lack of support and helps the abuse victim follow through on pressing charges.
Sam soon notices a bond between Alex and Luka. Though initially uncomfortable with Luka's involvement with Alex, Sam eventually accepts it and becomes good friends with Luka. Later, a romantic relationship develops. Unexpectedly, Alex's father, Steve, returns and attempts to push Luka out of their life. When she discovers Steve might stay permanently, Sam panics, packs up, and runs away. Before doing so, however, Luka runs to her, trying to get information from her as to why was she is doing this. Ignoring him and his slams on the car, fighting tears, she drives away. Sam has had a history of picking up and moving around the country to escape Steve. She worries that he will ruin her and Alex's life and that they cannot coexist with Steve.
She does come back thanks to Luka who finds her at a motel and brings her back. They move in together. Throughout season 11, Sam and Luka lived together, and Luka was a surrogate father for Alex, even going and meeting with a school official after Alex got caught with an issue of MAXIM magazine. At the end of season 11, Alex runs away to find Steve, by hitchhiking after a confrontation with Sam. He is out to find Steve in Colorado, even though Sam has hidden the fact Steve is there because he's in jail on robbery charges. Luka and Sam are frantically searching for him in the opener of season 12. Sam is desperately worried about Alex because of his diabetes, and his lack of insulin could have resulted in a coma or even death. Sam immediately gets in the car and drives non-stop to Colorado. Luka worries about Sam because they have been driving non-stop, and even hit a deer which completely destroys the windshield. Sam and Luka finally find an exhausted but stable Alex at a Canon City hospital, where he claims he's okay and that he knows how to take care of himself. After a tense conversation about Sam and Luka's relationship and their future together, they get to agree to disagree that Luka wants more kids and that Sam doesn't, saying that "I'm done having kids." She breaks up with Luka soon afterward and moves into her own place with Alex. Alex's father is then transferred to a jail in Illinois. In the Christmas episode, she lets Alex visit his father in jail after finding out he's been telling a friend that Steve is dead.
Later in season 12, a very wealthy patient named Richard Elliot, played by Armand Assante, enters the ER. He suffers from a debilitating disease in where he needs an in-home nurse. He takes a liking to Sam and offers her the position of head nurse. He reassures her that she would still be able to keep her job in the ER while being his in-home nurse. Since the offer was being an in-home nurse, he invited her to live in a section of his mansion for convenience. She denied at first, but later on, she finds out that Alex cannot be in the tutoring program because of the lack of funds. She arrives at the man's house, and asks if the offer still stands.
She has now moved into the mansion with Alex and is living a good life. Sam even took a chauffeured ride to work, causing her co-workers to speculate. Luka even inquires about how she is, probably curious to learn more.
In the 12th season finale, "21 Guns", Steve, a medical assistant named Mary and another prisoner named Rafe hatch an escape plot: Steve and Rafe injuring themselves and then escaping from the hospital. They stab Luka with a syringe as Sam looks on in horror. Because the syringe contained a paralyzing drug that would have led to his death, Sam steps in and treats him in spite of the prisoners' threats, saying she is going to make sure he doesn't die regardless of what they say; Steve makes his partners back off long enough for Sam to intubate Luka. They proceed to start shooting throughout the hospital once police catch on, using Sam as a hostage. Abby Lockhart and Jerry Markovic are hurt in the shooting. Steve drags Sam outside, towards the getaway van. She begs him, "Think about Alex!" but as it turns out, he already had, and Alex is tied up inside the van. Sam immediately gets in the van after seeing Alex, and later, Steve tells her that God spoke to him, and told him he had to get his family back together. With Sam and Alex as hostages, the three attempt to make an escape to Canada.
However, in the 13th season premiere, "Bloodline," the escape hits a few obstacles; Sam attempts to get help, and a police officer chases after the group, ending with the officer's (presumed) death. As the three argue about the escape plan, Steve shoots and kills Rafe and Mary, leaving only Steve, Sam and Alex. Steve tells Sam that he would rather have himself, Sam and Alex dead than apart, and then proceeds to rape Sam. Some time after, Sam, lying next to a sleeping Steve, proceeds to make her getaway with Alex. As she is about to escape, however, she returns to the still sleeping Steve, grabs his gun and kills him.
The next morning, she and Alex drive back to Chicago. Tired and panicked from her ordeal, she contacts Richard Elliot, who gets her an attorney, and instructs Sam to tell everyone she was raped by Steve and later killed him in self-defense. Despite an assistant District Attorney's suspicions that Sam is lying, Elliot, through his close friendship with highly-placed city officials, manages to get Steve's death listed as a justifiable homicide, thus ending Sam's legal troubles, although the ordeal's emotional toll on Alex is currently unknown. In "Somebody To Love", Alex tells Sam he saw her shoot Steve to death.
In the remaining episodes of Season 13, Alex results in telling his friend that his dad will die, relating to the trauma of his own dad's death. He also steals a credit card from Archie Morris, and (accidentally) sets their house on fire by playing with alcohol, which also leads Sam to terminate a budding relationship with a kind-hearted male nurse. Sam reluctantly sends Alex to a school for at-risk youth, and reports to her ER colleagues that he is doing better every day. She also bonds with a dying photojournalist and meets a handsome Chicago cop named Lichtman. In "In A Different Light", she meets the cop again at a speed-dating event and they leave together, starting to officially see each other, while she has also shown romantic interest in a hospital coordinator named Ethan and enjoyed some flirtations with Dr. Gates. She has since began a sexual relationship with the latter, which hit speed bumps when Sam was hostile to his friendly behavior on the job, but recovered when she decided to be more warm towards him than she'd been to previous love interests. Professionally, Sam has started training as a flight nurse.
At the end of "The Chicago Way," either Samantha or Dr. Greg Pratt entered a booby-trapped ambulance. The subsequent explosion resulted in a season-ending cliffhanger.The Season 15 opener, Life after Death, revealed that Dr. Greg Pratt was in the ambulance and later died from injuries sustained in the blast.