Season 4 begins with a drug-addled and deathly ill Frank reappearing. Meanwhile, Fiona cares for the household and works at Worldwide Cup with her boyfriend boss Mike Pratt, and attempts to connect with Debbie and Carl, who are dealing with the upheaval of their adolescent hormones.
Fiona is involved in a road rage incident that damages a company car and leads her to tell a lie about how it happened. Meanwhile, Lip struggles in school and with the ladies.
Frank stalks his previously unseen daughter Sammi and is surprised to learn that she has a son. Meanwhile, Fiona and Mike get serious; and Carl steals dogs and holds them for ransom, so he can earn some drug money for Frank. Also: Sheila has her first successful online date with a Native American cowboy named Roger Running Tree.
Fiona continues her secret affair with Robbie, but her infidelity is threatened to be exposed when Mike shows up at Robbie's apartment while Fiona is there. Meanwhile, Frank tries to contrive an "accident" that will net him a big insurance payout, so he can afford a potential liver transplant.
Fiona's series of bad decisions involving Robbie finally boil over. Meanwhile, Frank and Sammi pursue a cure for Frank's liver trouble and try to catch up on missed father-daughter time; and Lip gets a surprise visit at college from Army investigators.
The aftermath of Liam's accident lands Fiona in county jail, unsure of Liam's condition or her future. The family, minus Frank, wait nervously for any update on Liam's status at the hospital. Meanwhile, after almost being killed by the sweat lodge, Frank wakes up in the emergency room and gets some sobering news about his declining health.
Lip is faced with being the Gallagher's guardian when Fiona is released from jail and ordered by the court to remain inside the house, and Frank continues to be out of commission due to his illness. Fortunately, he gets some unexpected assistance from Amanda, his roommate's girlfriend.
Fiona rids the house of all suspicious items to prepare for a visit from her probation officer, but her efforts aren't appreciated by Debbie and Carl. Meanwhile, Ian gets kicked out of Mickey's house by a hammer-wielding Svetlana and makes a long-awaited return to the Gallagher house.
Carl connects with a troubled girl in detention; Lip grows close to his roommate's ex-girlfriend; Debbie tries to make life miserable for the new girl in Matty's life; Fiona struggles to get a job now that she has a criminal record; Sheila returns from her trip to the reservation with plans to adopt Native American kids; Mickey ignores the birth of his son to spend time with an erratic-behaving Ian.
Fiona goes wild and violates multiple terms of her probation by partying with Robbie's degenerate friends. A search for her gets underway when she fails to contact anyone.
Fiona is taken to a correctional facility; Frank wakes up from his operation suffering from post-operative delirium; Ian crashes the christening for Mickey's son; Amanda's parents bribe Lip to stay away from their daughter; Debbie meets an older student with a dark ulterior motive.
Season 4 ends with Sheila fighting for custody of the Native American kids and clashing with Sammi over where they will all live once Frank is released. Meanwhile, Fiona passes a drug test, gets released from jail and lands a job at Patsy's Pies with the help of her parole officer; and Frank begins to feel again like his old, troubled self.