- Anna Gunn as Skyler White, Walter's wife who was pregnant with their second child before his diagnosis and who becomes increasingly suspicious of her husband after he begins behaving in unfamiliar ways. Gunn sees Skyler as "grounded, tough, smart and driven". Gunn sees Skyler's stalled writing career as her biggest dream, saying, "I think she really deep down yearns to be an artist and to be creative and productive."[11]
- Aaron Paul as Jesse Pinkman, Walter's cooking partner and former student. Paul sees Jesse as a funny kid. "He's just this lost soul – I don't think he's a bad kid, he just got mixed in the wrong crowd." Paul elaborated on the character's background, saying, "He doesn't come from an abusive, alcoholic background. But maybe he just didn't relate to his father, maybe his father was too strict and too proper for Jesse." Paul compared the character's relationship with Walt to The Odd Couple.[12]
- Dean Norris as Hank Schrader, Walter and Skyler's brother-in-law via his marriage to Skyler's sister, Marie. Hank is a DEA agent. At the beginning of the series, this character was intended to be the "comic relief".[13]
- Betsy Brandt as Marie Schrader, Skyler's sister and Hank's kleptomaniac wife. Brandt described Marie as "an unpleasant bitch", but also stated that there was more to her than that. "I think we're seeing more of it now that she would be there for her family. But it's all about her."[14]
- RJ Mitte as Walter White Jr., Walter and Skyler's son, who has cerebral palsy. He begins lashing out after Walter's cancer announcement. Mitte himself has cerebral palsy, although his is a milder form.[15] Mitte stated that he had to regress from his therapy to portray the character, staying up late into the night to slur his speech and learning to walk on crutches so that his walking would not look fake.[16]
- Giancarlo Esposito as Gustavo "Gus" Fring (seasons 3–4; guest season 2), a Chilean high-level drug distributor who has a cover as an owner of the fast-food chain Los Pollos Hermanos. Esposito stated that for the third season, he incorporated his yoga training in his performance.
Gus is the coolest cucumber that ever walked the Earth. I think about Eddie Olmos way back in Miami Vice. He was like dead – he was hardly breathing. I thought, how is this guy just standing in this fire and doing nothing? Gus has totally allowed me that level of flexibility and relaxation – not because he has ultimate power and he knows he can take someone's life. He's just confident.[17]
- Bob Odenkirk as Saul Goodman (seasons 3–5; recurring season 2), a crooked strip mall lawyer who represents Walt and Jesse. Odenkirk drew inspiration for Goodman from film producer Robert Evans.
I thought about Robert Evans because I've listened to The Kid Stays in the Picture on CD. He's constantly switching up his cadence and his delivery. He emphasizes interesting words. He has loads of attitude in almost every line that he says. So when I rehearse the scenes alone I do my impersonation of Robert Evans to find those moments and turns. Then I go out and I do Saul.[18]
- Jonathan Banks as Mike Ehrmantraut (seasons 3–5A; guest season 2), works for Gus as an all-purpose cleaner and hitman, and also works for Saul as a private investigator. The character of Mike has been compared to Harvey Keitel's Winston Wolfe character in Pulp Fiction, which Banks says he is not trying to emulate: "I immediately tried to put it out of my mind, quite honestly. His cleaner ain't my cleaner. But throughout this world, you would suspect there had been a great many cleaners, whether government-run or individual contractors."[19]
- Laura Fraser as Lydia Rodarte-Quayle (season 5B; recurring season 5A), a high-ranking employee of Madrigal Electromotive and a former associate of Gus Fring. She reluctantly begins supplying Walt and Jesse with methylamine and helps Walt expand his operation overseas.
- Jesse Plemons as Todd Alquist (season 5B; recurring season 5A), an employee of Vamonos Pest Control who becomes an associate of Walt and Jesse.
