The series was defined by specific familes who lived in Chatsworth, including the Gallaghers, the Maguires, the Karibs, the Jacksons, the Crokers, the Fishers, the Powells, the Meaks and the Blancos.
- Lip and Ian Gallagher: The brothers were born a year apart and had a close, love-hate, based relationship. Lip was the first in the family to discover Ian's homosexuality, and agreed to help Ian keep it a secret, despite his own expressed misgivings.
- Debbie and Liam Gallagher: After the departure of Fiona, and the continued negligence and absence of both parents, Debbie would step up as her little brother's primary care-giver and role model. Despite the fact Debbie was forced by circumstances to grow up quickly, she never appeared to resent the role of acting as Liam's mother. Liam in turn would look up to Debbie and learn much from her, before he was compelled to take over the running of the Gallagher household when Debbie left for the army before Liam's elevanth birthday.
- Jamie and Shane Maguire: Ever since Jamie completed his prison-term, Shane saw Jamie as an unwelcome presence in the family business, even though Jamie was initially committed to going straight. However, several years later, in the wake of the breakdown in Paddy and Mimi's marriage, Jamie resolved to keep the family business afloat by taking over the overall leadership, due to the incompetence of his brothers, Shane and Mickey.
- Shane and Mickey: The two younger sons of the Maguire family are often seen at each other's throats, no matter how trivial the grievance is.
- Patreesha St Rose and Avril Powell: Patreesha would treat her younger sibling in a condescending manner, in which Avril would often quietly endure, though she would lash out on occasion when pushed to the edge by her sisters constant disrespect.