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Revolves around the lives of four close-knit sisters of Italian descent, raised in Brooklyn and now living in New York City.

Six friends come together for their 20th high school reunion in which one of them is murdered and all of them become suspects. A detective traces their turbulent and secretive lives back spanning 20 years to find which one had the motive.

A pair of college students discover they have a knack for solving crime.

Ginnie tells Danny that Ann is really depressed, but when Ann hears about it from Danny, she gets angry at Ginnie. Rose uncovers a shocking secret about Flash's past which gives Rose a chance to extort her. Marjee gets a new job.

Renee gets upset when it is suggested that she should see a therapist, but eventually she confides in Ann. Bob buys a car without consulting Ginnie. Marjee tells Jason that them sleeping together "was a one-time thing" because he is her boss' boyfriend. Joel apologizes to Rose and she accepts. Joel tries to come along with Alex, but it just isn't working. Things come to a point where Rose learns a lesson or two about men. Jason lends his car to Marjee, who tries to teach Ginnie how to drive.

Ann is ashamed to admit to the others that she slept with the much-younger Zach. Worse still, she left her phone in his dorm room and when Rose refuses to help her get it back, Ann's only option is to "return to the scene of the crime." Rose suggests that Ann invite Zach to Thanksgiving dinner since his parents are gone, and Ginnie and Marjee encourage this. It's Renee's first Thanksgiving with the Sorellis and she has offered to cook the dinner; the girls aren't willing because it would break the family tradition of preparing the meal according to their late mother's recipes, which they have maintained to honor her memory. When they tell Renee, she offers to help them uphold the tradition, and they reluctantly accept.

Ginnie and Bob decide to take a tour of New York now that it's still possible before Ginnie gives birth. Rose has a crush on a hunk in her class, Alex. Marjee is trying to get Ann to come to terms with the breakup while she herself is trying to survive having had to move back home.

Christmas is coming, as are Bob's parents--which he doesn't mention until two days before they come. Marjee's boss Trish also has a surprise announcement: she is seeing Jason and now that the "secret" is out, Trish can make out with Jason in front of Marjee. She can't take it and breaks up with Jason. When the sisters gather, Rose reveals that Joel kissed her and now she can't choose between him and Alex. Her sisters have their opinions: Ann votes for Joel, Marjee for Alex, and Ginnie for someone who is a mixture of the two--like Bob. Then someone anonymously sends Rose an iPod with her favorite songs in it. Ann has trouble not telling her dad what Renee told her confidentially.

Joe asks her daughters to take care of the deli while he is away for one weekend. Ann doesn't want to, but the others force her into it. Her reluctance vanishes when she meets handsome Marco, who works there. Marjee urges her to have a fling with Marco but Ginnie is against it, fearing that Ann will end up with a broken heart. Rose has trouble accepting harsh criticism from her acting teacher. The other sisters mistake Joel for her boyfriend, and Rose corrects that they are "just friends". Somehow that doesn't sound quite true... Ginnie takes charge at the deli, which Marjee doesn't like, and her repressed resentment against Ginnie surfaces just before the night of Marjee's party which takes place at her dad's place.

Alex finds out that Rose is trying to decide on the perfect time and romantic place for her first time. Ann decides to abstain from men, then Marco calls her... Bob is working overtime all the time so Ginnie decides to take some food and wine to him--and finds out that Bob forgot to mention that he's working with his ex... Jason has a plan about how to break up with Trish and stay with Marjee, but before he can execute his plan, Trish assigns Marjee to investigate to whose blocked number Jason has been making lots of calls... Joel literally turns his back to Rose; she realizes that it bothers her and she's really scared of losing his friendship forever. Alex sees what's going on since he's been in Joel's position, and he actually teaches naïve Rose another important lesson about men and women.

The sisters find out that their father is getting engaged and decide to arrange a surprise party for him, but they're in for some surprises as well.

Ann tries desperately to find a date for Justine's wedding, since Danny is no longer accompanying her. Rose's college friend Zach seizes the opportunity and volunteers to be Ann's date, but she has trouble accepting the age difference between them (suspension of disbelief is required of the viewer, since the actors are only 15½ months apart). Rose turns to Marjee for advice on how to have sex, although Marjee is probably the least-qualified one to give proper advice on the subject. A doctor tells Ginnie and Bob that they should abstain from having sex for 14 days, but that they absolutely do not want to do..

Ginnie and Bob almost get hit by a falling air conditioner, which causes them to decide on their organ-donor testaments, burial methods, guardianship of their orphaned children, and so forth. What they can't agree on is the guardian question. Marjee is trying to keep seeing Jason behind Trish's back. Rose goes to thank Joel for the gift and ask why he kissed her. Joel finally reveals everything. Ann is going to a therapist but avoiding the subject of fear of being alone. Her therapist suggest that she try to spend one evening totally alone, but her attempt fails when Zach calls her and invites her over for tequila and sex. Joe hires Marjee to plan his and Renee's wedding. And all this in just the first 15 minutes.

In the present, someone tries to murder Detective Marjorino by running him over with a car in a dark alley that will send him straight to the hospital. Will is on the scene and accompanies the detective in the ambulance. Back in 1995, Samantha and Craig set Will up for a blind date with Katherine Clark. The four of them have supper at Samantha and Craig's loft. Will and Katherine seem to hit it off. But Will's smile will soon vanish when he learns more about Katherine's family... Meanwhile, Carla gets a proposition she can't refuse. Aaron and his wife, Pascale, go to couple's therapy. Also, Jenna learns one of Brad's secrets.

In the present, Craig learns that his mother has died, and decides to attend her funeral. Also it's discovered that Henry is the one responsible for attempting to murder Marjorino, fearing he would get too close to a strange secret... but apparently not involving Samtantha's murder. Back in 1996, Will meets with Katherine's congressman father. The three of them go hunting together, which results in a fight between Will and the Congressman when something horrible happens and Katherine's father is killed. Meanwhile, Carla and Jenna are at Samantha's house where they talk about Katherine and Will among other things. Carla and Peter are trying to have a child, after their recent elopement. However, while working at the hospital, Samantha receives some test results for Peter, which seem to say he has leukemia. Single father Aaron has to take care of 13-month-old Noelle and five-year-old Chloe and also cope with work. After a hectic day and many problems, he calls on one of his best friends to help him out: Jenna.

In 1997, after Pascale left Aaron, it seems Jenna moved in to help take care of Chloe and Noelle. When Pascale comes back and wants custody, a court battle ensues. During the trial, it becomes apparent that while Jenna was living with Aaron, their relationship was not totally platonic. Meanwhile, Carla is at the hospital with Peter, who is sick with leukemia. The doctor informs them that the chemo is not working, but a bone marrow treatment can be quite affective. Carla meets with a medical claims offer who explains bone marrow treatment is not affective. However he insinuates that if Carla were to sleep with him, he could find a way to get her the money. Carla is thoroughly disgusted and calls Aaron to ask for money. Aaron says his assets have been frozen due to Pascale's paternity suit. Carla finally decides giving the claims officer what he wants may be the only way to save her husband. Contemplating what she is about to do, Carla receives a call from Aaron saying his assets are unfrozen and he has money they can borrow. Finally, Will learns the truth about Amy that she is the product of his and Samantha's tryst 11 years earlier.

Ginnie's doctor tells her to stay in bed until the end of her pregnancy to avoid premature labor, which means missing her dad's wedding. Bob solves this by attaching a webcam onto his head so Ginnie can see the wedding live. Marjee has arranged her dad's surprise honeymoon trip and asks the others to contribute to the $4,000 expenses. A movie is looking for extras and Rose wants to try to get in although her acting teacher explicitly forbids it. Alex is against the idea--until he suddenly gets a speaking role. Ann insists that Danny come to the wedding, then realizes that there might be an awkward situation. The girls get to meet Renee's son Patrick's boyfriend, and Marjee has a huge problem with Patrick: he too has a honeymoon surprise for Renee and Joe.

Ginnie's had it with Bob's hot ex Kylie staying at their place, but who's gonna tell her to leave? Ann is worried that Marjee is fleeing her feelings for Jason. When the girls gather, Rose immediately blurts out that she had sex with Alex. Meanwhile, Dad goes looking for Rose and finds Alex in her student apartment instead... Anne confesses to Marjee that Marco takes her breath away and that he wants to commit to her but she doesn't believe that their relationship would last. Marjee then gets the impulse to spend an evening with P.J. to take her thoughts off Jason. Alex tells Rose that he "hit it off" with Rose's dad and Rose makes the not-quite-safe decision to invite Alex to dinner.

Ann must hide Danny from Marjee, who is living with her. Bob generously offers to stay in with Ginnie since she must stay in bed. Ginnie orders him to go do something and invites Marjee, Rose, and Ann to play cards. Ann declines and must lie about being with Danny. Then all the other sisters hear that Ginnie has been taken to the hospital because her abruption of placenta has progressed. When Danny and Ann arrive at the hospital together, she spills out the story. Ginnie then has the genius idea to ask to see Danny and force him to tell what's going between him and Ann, but before she can interrogate him, things suddenly turn very serious when she has complications.

Weeks later, Marjee and Jason have got their business running. They try to keep their relationship professional, but their clothes just keep falling off... Bob has bought a watch as an anniversary gift for Ginnie, but Ann points out that Ginnie already has the exact same watch and promises to choose another present for Ginnie on Bob's behalf. Ginnie runs into a cute stray dog on the street and cannot resist bringing it home with her. Chloe and Joel get into an argument at a party and unfortunately Rose is also there.

Jason suggests that he and Marjee start a business together--just a business. But they discover that no one will work with them, thanks to Trish. And she will not forgive them. Bob and Ginnie's anniversary is approaching, but she is distancing herself from him; not surprising since he has managed to forget to mention to his parents that Ginnie lost their baby. Joel hasn't returned Rose's calls. When she catches up with him, she says she happy for him and Chloe. Joel then continues distancing himself from Rose--until he asks her to go see a movie with him. And she says yes. And Chloe is very upset about this. And Joel doesn't want to screw up the relationship with her, so he tells Rose that they cannot hang out again. Danny is--you guessed it!--distancing himself from Ann. She confronts him and it turns out that the abortion she did not manage to tell him about at first now threatens to break them up for good..

Trish has been sub-letting her apartment to Jason and is now kicking him and Marjee out of it, so they go to Ann's place. Joe calls Ginnie from Cape Cod and invites her and Bob there. Rose finally realizes that she loves Joel and breaks the "news" to her sisters, who have known all along; since Joel now has a girlfriend, Rose has only one option: to suffer. And suffer she shall, because Joel invites her to his birthday party. As for Marjee, Ann and Ginnie feel that she should protect herself from Jason now that he is her business partner. Also, they don't like him much. The argument ends with Marjee storming out.

Joe is moving to Cape Cod, but hurts his back while moving things. Jason suggests that he and Marjee move together. Rose goes to apologize to Joel and Chloe, but it's too late; Chloe has already broken up with Joel, who is unwilling to forget that Rose did not want him when he confessed his feelings to her, she only started wanting him when he became unavailable. Bob has been offered a position of a sound engineer on a tour with Kylie, but Ginnie thinks it might be the end of their marriage. The girls go through old stuff that triggers memories. Then they find a letter that unveils a secret from their late mother's past.