Saffron grows impatient with Edina's unwillingness to have their kitchen remodelled after Patsy accidentally burnt it down. Edina's obsession with finding a particular door handle for the kitchen leads her and Patsy to New York City. After a shopping spree, Patsy persuades Edina to have her navel pierced. Edina finally finds and photographs the door handle at the Four Seasons Hotel. Upon returning home, Edina not only fails to notice that Saffron has had the kitchen refurbished in her absence, but learns that she has forgotten her daughter's birthday.

As Edina and Patsy prepare to attend an underground rave on New Year's Eve, they receive an unexpected visit from Patsy's long-lost older sister Jackie. Patsy insists on taking Jackie along to the party, much to Edina's dismay. However, Patsy is disappointed to learn that Jackie is no longer the jet-setting, drug-addled party animal she used to be. Now homeless, Jackie asks Patsy if she could stay with Edina until she can raise money to open a shelter for stray cats and dogs. After helping Jackie loot Edina's bedroom for valuables she can sell to raise money, Patsy throws her out of the house, but it is too late to go the party a frustrated Edina has fallen asleep in the sitting room, surrounded by her family as the clock strikes midnight.

Patsy convinces Edina to hire two male prostitutes (through Edina's hairdresser Christopher) for an orgy on the night of Saffron's university presentation. However, Edina is unable to loosen up, and the prostitutes are not particularly enthused, either. Patsy attempts to enliven the mood by playing a video of an orgy she and Edina attended in their youth, only to find that it has been accidentally switched with a tape of Saffron's school project. Fearing the worst, Edina and Patsy accompanied by Mother, Christopher and his drag-queen boyfriend rush over to the university, though not soon enough to prevent a mortified Saffron and her classmates from watching the orgy tape, which shows couples having sex while Edina is asleep.

Edina becomes frustrated when she loses a prestigious PR award to rival Claudia Bing, despite having bribed the judges. Worried about her dwindling career, Edina works on a campaign in hopes of upstaging Claudia. Meanwhile, Saffron becomes romantically involved with Gerard, her psychology lecturer, until she discovers that he is married with children. In a rare occurrence, Edina comes to Saffron's aid by punching Gerard in the face. At an industry luncheon, Edina's speech is stolen, prompting a drunken rant against the bastardisation of the PR industry, which proves a success. When Edina and Patsy attempt to retrieve the speech, the duo awaken the next morning on a trash barge headed for Ostend.

Edina is left feeling helpless after Saffron leaves home to attend university. Patsy loses her job when Ella magazine folds; she later receives an offer to work with her colleague Magda at a New York magazine. Edina and Patsy commiserate drunkenly with each other over old age and the sudden changes in their lives. Saffron returns for a visit, appalled at their behaviour. When Edina announces plans to sell the house before embarking on a journey of self-discovery, a livid Saffron storms off. Edina's plans also mean that she is cutting off Patsy. Embittered, Patsy leaves as she decides to take the job in New York.

Edina joins a New Age commune, but she struggles to fit in and quickly becomes bored. Patsy finds herself disillusioned with her new job in New York due to creative differences with her co-workers. Saffron settles into university life and Mother spends her days at the Monsoon house, drinking champagne and ordering items from the shopping channel. After realising that their lives are not the same without each other, Edina and Patsy happily reunite on top of Carnegie Hall Tower before returning to London. Back home, Mother has been arrested for squatting and credit card fraud. A flashforward to 25 years into the future provides a glimpse into the lives of Edina, Patsy, Saffron and Mother.

Saffron accepts a marriage proposal from Paolo, her pompous, controlling Italian boyfriend, to Edina's shock. Edina and Patsy travel to a ski resort in Val-d'Isère, France, but they are disappointed by the lack of celebrities in town. Later, a drunken altercation ensues when Edina points out their constant dependency on each other, destroying their chalet in the process. The next day, Edina loses control while skiing and nearly falls over a cliff. In a near-death experience, God (in the guise of Marianne Faithfull) appears to Edina in heaven, informing her that it is not her time yet. Back in London, Mother is brought home by a disguised Bo—who is hiding from Scientologists—after being mistaken for a terrorist at the airport, and realises she has forgotten to collect her American friends, Mac and Millie.

Edina and Patsy return home from Val-d'Isère. Upon discovering that Paolo's parents are wealthy and famous, Edina takes a sudden interest in Saffron's upcoming wedding. When Paolo's parents come to visit, his mother, Kalishia, disapproves of Saffron and refuses to allow Paolo to marry her. Patsy blackmails Kalishia into changing her mind by reminding her that they once co-starred in a Bond-inspired pornographic film. On the wedding day, Edina replaces Saffron's bridesmaid, Sarah, with Georgina, a Gucci model. When the vicar asks if there are any objections, Edina has another vision of God, who opposes the marriage. Edina interrupts the ceremony, prompting the guests to leave, while Paolo departs with Georgina. Though initially devastated, Saffron ultimately admits that Paolo was not right for her, before Edina and Patsy reveal that they are going on her honeymoon trip.