"It's Good To Be Back!"

• Nov 4, 2008, 04:11 AM ET
• by Shawna Malcom

It's a mid-October afternoon on the set of the ABC comedy Samantha Who?, and Christina Applegate is doing what comes naturally: making people laugh. As the cameras roll, the actress, seated at a large wooden table in a warmly lit dining room, sifts through a white box overflowing with mementos from a teenage rock-star crush her amnesiac character can't recall. The chemistry between Applegate and her costars—recent Emmy winner Jean Smart, Kevin Dunn and Melissa McCarthy, who play Sam's parents and wide-eyed friend, respectively — is palpable. But what really makes the scene crackle are the witty bits of improvisation Applegate nimbly tosses into each take. One line in particular — "Who are the John — us Brothers?" — sends both cast and crew into hysterics once the director yells cut.

"It's good to be back," Applegate says later, curling up in a cozy ivory armchair in her spacious dressing room and tugging the sleeves of her gray wrap sweater over her hands. "I get tired quickly. But it's nice to have a focus for a minute outside of that."

That, of course, is her recovery from breast cancer. The 36-year-old actress was diagnosed in late March and ultimately underwent a double mastectomy in July. Applegate is now cancer-free and, slowly but surely, healing both physically and emotionally from an ordeal that she admirably makes no effort to sugarcoat. "I still have quite a process until this is done," says Applegate, who will undergo reconstructive surgery in late November, around the time of her 37th birthday. "Yes, it's hard. It sucks. But I'm not a victim."

Not surprisingly, Applegate is a profoundly different woman from the one who last sat down with TV GUIDE a little less than a year ago. Then, she lived and breathed her work, almost to the exclusion of everything else. It had been that way for much of her career since she got her big break, at age 15, as clueless Kelly Bundy on Fox's Married…With Children. While she gamely ticked off a list of goals for 2008—traveling, getting massages each weekend—it was clear that the one she was most committed to was working on either a film or play during her summer hiatus from Samantha Who? Downtime, balance, treating herself with the same TLC she heaped on close friends and the coterie of pets (three cats, a dog and two turtles) with whom she shared her Hollywood Hills home? Those things would just have to wait.

All of that shifted early last spring. "I started looking for a beach house the day I found out I had this little disease," Applegate says. "You just kind of go, 'What are you waiting for to get the things that you want and the things that you dream of?'"

She bought a "peaceful, quiet, beautiful" place where she spent three weeks recuperating postsurgery surrounded by friends and family, including her mother, actress Nancy Priddy, who had also bravely battled—and beaten—the disease. "I really allowed myself to fall into their care, which is very hard for me because that's not my personality," says Applegate, who now tries to spend most weekends at her beach retreat. "To go, 'OK, yeah, you can grab me that coffee from upstairs because I just can't do it right now' was big for me."

Applegate needed a strong support network more than ever. Besides her medical issues, she was also grieving the loss of two beloved cats and her ex-boyfriend Lee Grivas, who died of an apparent drug overdose on July 1, only a few weeks before she underwent surgery. "To be honest, I think that was even more difficult and more painful than anything else," she says of Grivas' death, before adding quietly, "It still is a lot of the time."

Returning, then, to the Samantha set in September for Season 2 was a comfort. The show was one of last season's few breakout hits and earned Applegate both Emmy and Golden Globe nominations. This season, expect to see Sam's romance with millionaire Owen (Men in Trees' James Tupper), an avid environmentalist, heat up over several episodes. "He's essentially the perfect guy," says executive producer Don Todd. "It's about how much harder it is to date the perfect man than you would think." Also look for Mary-Kate Olsen to wreak havoc in the November 10 episode as a troublemaker Sam meets while doing community service. Sam will want to help her, in part because the young woman reminds her of her pre-amnesia bad-girl self. "I think I'm bringing a lot of me now to Sam," says Applegate of the character, who's still struggling to figure out who she is and wants to be. "Just in the sense of, 'This too shall pass,' you know?"

For more on Christina Applegate, pick up the new issue of TV Guide, on sale now.