Beatrice, who is the mother of four sisters - Alex, Teddy, Georgie, and Frankie- is thinking about selling their family home. Georgie is trying to deal with her unemployed husband, who wants to be a lounge singer, and two sons. Teddy returns after a three year absence to reclaim her ex-husband, who has moved on to her baby sister, Frankie.
Alex hires a private eye to see if her husband, Wade, is having an affair. Meanwhile, Teddy and her teenage daugher, Cat, move in with Georgie.
It's been one year since their father's death, so the sisters go to visit his grave. They gett there just in time to see a mysterious woman leave him a dozen red roses. The woman turns out to be his longtime nurse. Frankie soon discovers through her mother, what the nurse actually meant to him.
Georgie is nervous not just because her boss is coming to dinner, but because her husband still does not have a real job. Alex is upset because Wade has actually left her. Frankie arrives just in time to tell everyone that Teddy's ex-husband, Mitch, just asked her to marry her.
Frankie is finally going to get her wish, she is marrying Mitch. Alex is hosting the event, but Teddy is refusing to attend because it will be too painful for her. However, just as the guest are arriving, Teddy actually does show up, drunk and with a shotgun.
Georgie and her husband, John, find out that their son Evan has leukemia. Soon her sisters -- Alex, Frankie, and Teddy-- rush to be at her side. Meanwhile, Teddy decides that she is going to leave town.
John finally comes to his senses after Evan begins receiving chemotheraphy treatments for his leukemia. Alex plans an extravagant 10th birthday party for Evan, which Georgie disapproves of. Teddy begins trying to reconnect with her teenage daughter, Cat, who is now staying with her father, Mitch. Teddy starts drinking again and Georgie forces her to move out.
John begins receiving orders for his vocal tape as he tries to help Mitch save his fish market. Teddy meets Hank Seawell, a photographer, who takes picture of the homeless. Alex decides to spend more time with Wade and gets tickets to a theatre show. However, it turns out that one of the stars is having an affair with Wade.
Alex and Wade go to their lawyers to negotiate their divorce settlement. Frankie tells Teddy about her marriage to Mitch, but Teddy does not tell her that she is pregnant with Mitch's child. Wade discovers that his mistress hired a hitman to kill Alex.
Frankie and Mitch decide to make their marriage public. When Cat finds out she runs away which brings Teddy and Mitch together, but Teddy still has does not tell him about being pregnant with his child and even contemplates an abortion. Meanwhile Alex, still depressed over her failed marriage, decides she wants to be even more free-spirited that Teddy ever was.
It's time for Alex's high school reunion and she's nervous because of her recent divorce. Frankie finds a condom in one of Cat's schoolbooks. Bea begins dating Judge Truman Ventner. Georgie and John try to bring the passion back to their marriage.
Hank Seawell and Teddy prepare for his photography exhibit that is hosted by the Hospital Women's League and Alex is the chairwoman for. Wade makes an appearance and he and Alex end up making love. Teddy protests when nude photos of her are removed from the exhibit and is promptly arrested. Meanwhile, John gets insulted on a radio show and is not happy about it.
Trevor begins suffering from jealousy after Georgie misses his soccer game to take Evan to the doctor. Teddy finally tells someone she's pregnant, albeit Hank, who asks her to move with him to New York. As Teddy reveals to the family she is pregnant and leaves out that it's Mitch's, Hank goes to Mitch and tells him the truth. Meanwhile, Georgie and Alex accidentally walk in on Bea and Truman having sex.
The sisters talk Alex into joining a computer dating service. Although she refuses to go out with the computer match, she does end up on a date and in bed with her plumber, Victor. Georgie and John fight over a tree with their neighbor and he ends up chopping down with tree while Evan is in it. Frankie has to make a big effort to get along with her abrasive mother-in-law, Naomi Margolis.
Georgie ends up reliving Thanksgiving pasts as she prepares for the entire family to come to dinner and her son's medical test results. Meanwhile, Alex and Wade welcome home their daughter Reed from France.
Teddy faces another emotional setback. Reed and Alex enter a mother and daughter pageant together. One of Frankie's clients is a little too interested in her.
Christmas means it's time for the annual Reed family gathering at Georgie's. Frankie is upset when she sees Mitch comforting Teddy. Georgie finds out that the eggs she used for her yearly eggnog were tainted. Alex has decided that she is going to leave the annual celebration early to go to Mexico with Victor.
Georgie learns that Evan's home tutor, Jim, may be HIV positive. Although many of the parents want him to leave, Georgie speaks out for him at a PTA meeting, but Jim is forced to leave anyway. This causes Georgie to ponder running for the school board. Alex is upset because immigration has threatened to take away her longtime maid. Mitch gets audited by the IRS for a year that he was married to Teddy. After each deduction brings back memories of his old marriage, Frankie declines to help them through do the taxes.
Because she has so much work to do, Frankie decides to cancel her fishing trip with Mitch, but Teddy urges her little sister to put the work aside and go with him. Alex faces a dilemma when her hunky plumber and ex-husband both have awards banquets scheduled on the same night. Teddy finally chooses to buy a car, but it's not as easy as she thinks.
Frankie's assistant, Jill, claims that one of her client's representative's is sexually harassing her. Bea informs her daughters that she and Truman have decided to move in together. Teddy gets a job selling cosmetics, but ends up with another gig.
Georgie decides that she will run for the school board after all. Meanwhile, Alex is desperate for Reed to get into a prestigious' girls school, but Georgie's run for the board might hamper her chances.
Alex faces new competition for Victor, her own daughter. Teddy takes some of her clothing designers to her former employer, who wants to put them in a show. Frankie and Mitch are desperately trying to conceive.
Georgie discovers that John's plane has crashed and the sisters rush to be at her side.
Alex meets her very own Prince Charming, while Georgie and John begin wondering about the passion in the marriage and Frankie and Mitch begin wondering if they can live happily ever after.
The sisters learn there is a fifth one Also, Frankie finally meets a nice guy, but despises his son.
Teddy decides to go to rehab, as Alex deals with being the Mayor's wife. Meanwhile, Frankie urges Lucky to withdrawl from his fight.
Georgie gives Teddy and Frankie some unexpected Christmas news. Meanwhile, Thomas George disappears from a Christmas tree lot.
Aunt Gigi visits and shares stories from her past about expectant mother Georgiana, bride-to-be Theodora, who wants to elope because her fiance is going off to World War I, and Alexandra who has stars in her eyes and longs to be famous.
Norma finally gives birth and gets an unexpected visit from her mother; Teddy is put of by Sorenson, who ends up asking her out and Georgie is forced to find new living accommodations after John kicks her out.
Alex and Charley become furious over Georgie's thesis; Bea's illness worsens as the sisters become closer.