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.