Lele Martini, a general practitioner with Rome's experimental local health authority, moves to a new home in Poggio Fiorito, a residential area just outside the Italian capital. He's accompanied by his father, Libero, who recently retired, and their children, Maria, Ciccio, and Annuccia. Maria is opposed to the move, but changes her mind when she meets Reby, a classmate who becomes her best friend.

The story picks up six months after the season one finale. Alice returns from Africa and begins a relationship with Lele. She also returns to work as a radio host on Radio Tua. After various ups and downs, Lele and Alice get married in Roccalta, with all their family members happily watching, except for Nicola, who lives in Brazil. The newlyweds are supposed to go on their honeymoon there, but Alice falls ill before their departure and is rushed to the hospital: she's had a miscarriage and is told she won't be able to have children.

The story picks up approximately three years after the season two finale. Lele, Alice, and the twins move to Australia, as he begins a research career. Libero then becomes the head of the family. Maria, fresh from high school, goes to university to begin medical school, where she meets the handsome and kind Dr. Guido Zanin, who has just arrived from Milan. Guido goes to work at the local health authority and rents Lele's room in the Martini household. He grows fond of everyone in the family and falls in love with Maria. Marcello, Guido's childhood friend, begins working at the radio station where Alice worked. Cettina, abandoned by Giacinto, begins a relationship with Augusto Torello, an undertaker: it is the first time a character in a fictional story has held this position.

The story picks up approximately three years after the season three finale. It's revealed that, during the narrative gap, Guido has been forced to work in Milan, and so he's constantly moving between the Lombardy capital and the Italian capital, having yet to secure a transfer to Rome. Libero and his three eldest grandchildren return from Australia, where they spent the summer with Lele, Alice, and their two younger grandchildren. Nicola returns to Italy to seek a divorce from Enrica. After some disagreement, she agrees to a consensual divorce and invests all her money in a business deal with her ex-husband, which, however, turns out to be a scam. Enrica thus becomes penniless and is taken in by the Martinis. Cettina and Torello move into the cottage next door to the Martinis', and Torello moves his funeral home into the new house.

The story picks up approximately three years after the season four finale. Lele lives in Paris, where he has become a university professor. Turinese doctor Emilio Villari, engaged to Alba, the daughter of Gualtiero, a cynical entrepreneur and longtime acquaintance of Enrica, arrives at the Martini household. An Indian family arrives in the neighborhood. There's Kabir, a traditionalist Hindu, a middle-aged man and grandfather of three grandchildren: Sarita, a doctor specializing in homeopathy who nevertheless lives by Western values, and the young Sadju and Sumede, the same age as Ciccio and Annuccia, respectively. Emilio has to open a semi-private health center in Rome: his future father-in-law tells him he can't immediately return to Turin because he must stay to supervise the proper functioning of the new healthcare facility. Only in the fifth season does Poggio Fiorito cease to be a neighborhood and become an autonomous municipality.

The story picks up about a year after the season five finale. In Rome, preparations are underway for Ciccio and Miranda's upcoming wedding. In Paris, Lele, a Sorbonne academic, has written a book. He comes to Italy with his two children, Elena and Bobó, intending to attend the wedding. However, Alice, from whom he recently separated, will not be present. Ciccio, Nilde, and Andrea Biglietti have opened a farmhouse in Puglia, agreeing with Miranda to move there after the wedding. However, she no longer wants to get married and leaves Ciccio, making him change his mind about Puglia as well. Lele decides to take a sabbatical from the Sorbonne to stay in Rome. Maria and Guido are expecting a baby, but they can't move into their apartment because the man who rented it refuses to vacate it and continues to live there without paying. Annuccia has entered adolescence and finds a new friend and her first love.

The story picks up approximately three years after the season six finale. Lele works as a doctor at the Villa Aurora clinic and as a professor at the University of Rome, but decides to give up this second job when he learns the university won't fund the trial of a drug for a rare disease. Libero has moved to America to be reunited with his brothers. Guido died in a car accident some time ago: both Ave and Maria are struggling to move on. Palù starts kindergarten and befriends young Jonathan, the son of journalist Marco Levi. A complicated love story develops between him and Maria, between her doubts as she is still processing her grief and struggling to start a new relationship, and him, who is very focused on himself, his work, and his son. Grandma Enrica hasn't followed her husband to the US because she runs a small business exporting artisanal products from Puglia.

The story picks up a week after the season seven finale. Grandpa Libero has returned to Italy. At the Martini house, Marco and Maria announce they are getting married. Lele is summoned by the bank, and goes with Bianca, who is pregnant (as revealed in season seven). The bank manager explains to the Martinis that all residents of the Poggio Fiorito neighborhood must buy back their homes or resign themselves to losing them. The wedding is postponed because the entire family must save to face the unexpected. Fulvio Magnani, a shady businessman, becomes an enemy of the Martinis because, unlike the other families living in the neighborhood, they refuse to sell their home to him. Bianca and Giulio interact with their mother, Gemma Aubry, who appears only in this season.

The story picks up nine months after the season eight finale. Libero addresses viewers directly, explaining that Lele and Bianca have moved to Paris, Dante and Melina to Sulmona, and Anna is in London for her senior year at a private college. Libero and Enrica are no longer tending Nilde and Andrea Biglietti's Apulian farmhouse and have returned to permanent residence in Poggio Fiorito. On a plane to Rome, they meet Lorenzo Martini, son of Achille (one of Libero's Italian-American brothers), and Sara, sister of Marco Levi. Unaware that they share in-laws, the two find themselves living under the same roof. Lorenzo is a doctor who begins working at Villa Aurora after a brilliant career in the United States, and is hosted by his uncle Libero.

On January 1st, a man rushes to the airport to leave, but he's late, and the plane leaves without him. The story picks up eight months later: in August, the Martini family is on vacation in Puglia, but without Bianca and little Carletto, who live in Paris with Gemma Aubry. The radio broadcasts news of the terrible plane crash on New Year's Day, from which the man fortunately survived. Maddalena, a longtime acquaintance of Libero, is abandoned by her father Gennaro. Libero and Enrica take her with them to Rome upon their return from vacation. Valerio Petrucci, the surviving man, wants to meet Elena, but is unaware that Lele's first wife has been dead for a long time. Elena and Valerio had been having an affair, and Valerio asks Lele to verify which of them is Anna's biological father, with whom he has since become friends.