Samantha wakes up in the hospital with no idea where she is or who the family and friends gathered around her are. Following the accident, Sam suffers from retrograde amnesia and has no memories pre-accident, but is able to fully function. To some this may be a curse, but for Sam it gives her a chance to rediscover herself and be a better person the second time around -- before the accident she was a horrible person, vain, selfish and had more enemies than friends.
In one single morning Samantha learns a lot about her old self, but still has no idea what she does for a living. When she witnesses a cutthroat board meeting, Sam debates whether or not her new self should return to that life. But Sam soon learns that not being able to remember her past doesn't mean she can escape it.
Thrilled in thinking that someone must have liked the former her, Sam quickly agrees to be a bridesmaid at a wedding. However, when Sam arrives at the wedding, she learns she's been uninvited by the bride. Despite being bummed by the rejection, Sam decides to turn it into vindication by apologizing and being reaccepted by the bride.
While out with Andrea, Sam realizes she has no memory of sex. Now that she's in essence a virgin, Samantha debates reexperiencing her 'first time' or waiting for the right guy.
While out with Todd, Sam runs into an old boyfriend and learns that he has a restraining order against her. After memories begin to flood back, Sam worries that her need for attention is a result of her poor relationship with her father. To fix this, she sets out to win her dad's affection, regardless of the steps it takes.
Sam has a session with a hypnotherapist in order to try to regain lost memories. But her revelations in session lead her to believe that Regina and Howard may not be her real parents. Meanwhile, Todd makes a confession to Sam.
Feeling that it's time for her daughter to start dating again, Regina shocks Samantha by setting her up on an unannounced blind date with Kevin, the contractor hired to refinish their floors. When Sam inadvertently leads Kevin to believe that she's an avid hockey fan, she finds herself turning to Todd for advice which is complicated by the fact that he has a new girlfriend, Chloe. Meanwhile, Andrea is psyched to be flying to Rome with her latest fling
After borrowing her father's car, Samantha gets into an accident and afraid of his reaction, tries to cover it up by pushing it into a lake. But guilt soon begins to consume her when her dad feels sorry for his little girl and ends up buying Sam another car, thinking his was stolen. Meanwhile, when Regina finds out what Sam has done, she blackmails her into being a model for her party.
Sam falls hard and fast for Kevin, and when she thinks that she may be in love with him Kevin begins to pull away, ultimately breaking up with her. In doing so, Sam's memories about her relationship with Todd begin to resurface.
When Samantha finds out that she could be evicted for subletting her apartment to Todd, she moves back in, but the timing could not be worse as Todd just invited his girlfriend to move in with him. Regina and Dena have a girls night at the house after Samantha doesn't show up as planned.
Samantha is shocked when Winston Funk, a wealthy man who owns a real estate firm, proposes to her. Sam realizes that since Andrea is completely in love with him, his proposal could ruin their friendship.
Sam reluctantly sets Dena with her boss, but uses her unsuspecting friend to try to convince her boss to shut down a contruction project that is endangering a butterfly habitat. Meanwhile, Sam tries to figure out why Todd is ignoring her after they kissed.
In order to make it seem like she's moved on, Sam asks Craig, a complete stranger, to be her date to Todd's gallery exhibit. However, Sam soon learns that she and Craig may have met sometime in the past and not in a good way. Meanwhile, Howard finds one of Todd's picture that shows his daughter in a not-so-positive light.
Samantha continues to have an affair with Todd -- who is still dating Chloe -- and begins to believe that her mother is having an affiar of her own. Meanwhile, Andrea considers opening a coffee shop with Dena.
Sam's relationship with Todd begins to move along too quickly leading her to put it on hold until Todd breaks it off with Chloe. However, Sam soon begins to think that Chloe is making up a story about a sick aunt in order to guilt Todd into staying with her. Meanwhile, Regina and Andrea clash over how best to plan Sam's birthday party.
Samantha and her mother team up for a dance competition in hopes of beating Regina's enemy, Paula Drake. However, the two soon find that "old" Sam could dance; "new" Sam clearly cannot. Meanwhile, Sam starts to enjoy her new life in her apartment, but Todd has trouble finding his own apartment.
Trying to find a new direction in life, Samantha decides to head to Africa in order to help the needy. However, her friends are sure she'll back out, especially after seeing the list of required vaccinations. To make everyone think she's out of the country, Sam must hide with Andrea and Dena.
After Dr. Andy gives Samantha pills as part of a clinical trial to help people with memory loss, she begins to regain multiple memory fragments -- all reminding her of how bad she used to be. But she discovers one pleasant reminder from the past that could have changed her life forever.
Meanwhile, when Andrea and Dena are mistaken for a gay couple, Andrea tries to prove that she could hook up with a much hotter woman than Dena.
In need of money, Samantha agrees to go into the real estate business with Regina. However, her first client, Owen, could end up taking her off her new path of morality. Meanwhile, Andrea tries to seduce Seth, Todd's friend, in order to get the phone number of a professional basketball player.
Samantha is arrested after having a run-in with a cop. While completing her community service, she meets Natalie, a troubled young woman, and takes it upon herself to help Natalie turn her life around. Meanwhile, despite Todd telling Howard he and Sam are just friend, Howard gives him advice on how to get her back.
Sam tells her current boyfriend that she is living with her ex-boyfriend, but Sam finds out that Owen's best friend is his ex-girlfriend, Willow.Confusing?, Wait it gets better...Willow has feelings for Todd and Sam is now jealous and is asking herself which guy does she want?
Meanwhile, in order to get the date with the hunky pro-basketball player, Andrea tries her best to shoot a flattering picture of herself, yeah right...tune in and find out what happens.
Sam's decision to invite Owen to dinner with her parents goes awry when Owen's thoughts about chicken farms hits Howard the wrong way. Meanwhile, Dena, worried Chase isn't spending enough time with her, sits in on one of his meetings; and Todd enjoys having the apartment to himself.
Samantha tries to be an environmentalist in order to impress Owen. Meanwhile, Andrea learns she's not on pro-basketball player Tony Danes' radar.
After getting her heart broken, Sam goes on vacation a family vacation with Andrea and Dena tagging along. While staying at a lodge, Sam must resist reconnecting with Brad, the lodge owner.
Sam and Todd go on a double date with Andrea and Tony Dane, but when Todd makes a discovery about Tony, Sam tries to interfere in order to keep Andrea from getting hurt. Meanwhile, Dena goes to Regina for help when she gets an online pen pal and worries that Chase will be jealous.
Sam feels like she wants to have a child, and borrows Dena's dog to see if she can be nurturing enough to take care of a baby. When Howard's late step-brother leaves him a plane in his will, Regina decides to take flying lessons. Andrea goes on another date with basketball star Tony Dane.
A series of misunderstandings has Sam believing she must improve her friendship with Frank. Andrea fears she will no longer receive the perks she has now from dating a basketball player now that he has been outed as gay.
Sam's ex-boss, billionaire Winston Funk, may help her out of a crisis when she looses all her money in Las Vegas. Meanwhile, Dena and Andrea both ask favors of each other.
Sam is willing to give Todd a second chance and offers him a "first date," but Todd won't trust Winston Funk, who has been wanting Sam o continue the affair they had before her accident. Meanwhile, Andrea goes on a reality show concerning celebrity weddings while planning her big day when she plans to wed gay basketball star Tony Dane.
Sam fears she may have cost Todd a career in photography as her old self, so she tries to make it up to him by sabotaging the work of his competition at a local newspaper. Meanwhile, in order to continue her Real Estate partnership with Sam, Regina puts Dena's home on the market...without telling Dena.
Samantha's stunned to find out she has an aunt and a grandmother, both which have never been mentioned due to their longstanding family feud over an heirloom.
Sam becomes the head of the charity foundation for Winston Funk and hires Andrea as her vice president of legal affairs. She soon regrets this idea when Andrea shirks her duties in favor of planning her wedding.
Sam decides to give Todd a second chance by going out with him on another "first date," but Todd doesn't trust Winston Funk, believing her trying to Sam to continue the affair they were having before the accident. Meanwhile, Andrea appears on a reality TV series about celebrity weddings, along with her gay basketball star Tony Dane.
Sam discovers that one person who played an important role in her life before the accident is Winston Funk's ex-wife. Meanwhile, Andrea attempts to seduce her gay fiance.
The series ends with Andrea's wedding, along with Sam deciding between Winston Funk or Todd. Meanwhile, Regina and Howard realize that their paths are moving in different directions.