Will this be the year Christina Applegate finally gets her SAG Award?

Fifteen years after her first nomination in 2008, the actress enters the 2023 Screen Actors Guild Awards on Feb. 26 a seven-time nominee. Applegate is up for Outstanding Performance by a Female Actor in a Comedy Series for her role of Jen Harding in Netflix's Dead to Me, joining The Marvelous Mrs. Maisel's Rachel Brosnahan, Abbott Elementary's Quinta Brunson, Wednesday's Jenna Ortega and Hacks' Jean Smart.

As Applegate previously noted, this awards show will be a particularly poignant event for her as she continues her journey with multiple sclerosis.

"It's my last awards show as an actor probably, so it's kind of a big deal," the 51-year-old told The Hollywood Reporter Feb. 8. "Right now, I couldn't imagine getting up at 5 a.m. and spending 12 to 14 hours on a set; I don't have that in me at this moment."

Applegate publicly shared her battle with multiple sclerosis on social media in August 2021, explaining she'd received her diagnosis a few months prior while working on the third and final season of Dead to Me.

"To be honest, being diagnosed with MS last year and what had happened to my body, to my mind, to my spirit, to my everything, of course, I didn't want to be around anyone or talk about it," the Samantha Who? alum said on a December episode of The Kelly Clarkson Show. "But I had to go to work. I was not forced to go to work, but I made sure that we finished the show. We had to finish the show. That was a part of my family. Linda Cardellini, Liz Feldman, everyone there is my family and there was a story that we needed to finish. And I pushed as hard as I could through that." 

Working on the series, she said, helped her navigate this new chapter of her life.

"The beauty of Dead to Me is that it gave me almost this weird platform of dealing with it," she continued, "where I didn't have to be on all the time, and I didn't have to make all the jokes, and I could fall apart in a scene and it was my soul actually falling apart unfortunately in front of the world. But it was cathartic in a beautiful way."

In honor of Applegate's most recent SAG Awards nod, here's a look back at a few more of her unforgettable roles from over the years.

Applegate played Kelly Bundy, the daughter of Al and Peggy Bundy (portrayed by Ed O'Neill and Katey Sagal) and sister to Bud Bundy (David Faustino), on Married...With Children from 1987 to 1997. But the actress, who was just 15 years old when she was approached for the role, almost didn't take it.

"I did not want to do the show," she recalled on The Rich Eisen Show in 2017. "At that time, I was on a drama series, and I thought it was disgusting. I wouldn't even audition for it. They went ahead and shot a pilot with two other kids. For whatever reason, the chemistry just didn't work, and they came back to me and said, 'Would you please come in?' And I was like, 'No.' They sent me the pilot, and my mom and I did not want to like it. And we turned it on, and we were stifling laughing. So, I thought, 'I'll go in.' But I'd never done comedy before."

However, Applegate ended up doing a lot more comedy. She starred in the 1991 movie Don't Tell Mom the Babysitter's Dead, in which her teenage character Swell starts running the household for her and her siblings after their mom heads off on a trip to Australia and—as the title suggests—the hired babysitter passes away.

After Married...With Children ended, Applegate continued her television reign with shows like Jesse, which ran from 1998 to 2000. Applegate received her first Golden Globes nomination in 1999 for her turn as title character, single mom Jesse Warner, who works at her dad's German bar.

The sweetest thing about this movie might be the real-life friendship that developed between Applegate, Cameron Diaz and Selma Blair.

"I'm still so close, obviously, with Christina Applegate," Blair told Entertainment Tonight in 2021. "Cameron always is Cameron Diaz amazement."

In the 2002, R-rated movie, Diaz's character Christina—whose BFFs are Applegate's Courtney and Blair's Jane—has no interest in entering a committed relationship until she runs into a man named Peter (Thomas Jane) at a bar. She and Courtney then decide to take a road trip to a wedding where Peter will be to see if he's the one.

There was also the one where she played Amy Green, the sister of Jennifer Aniston's character Rachel Green, on Friends. While Applegate only appeared in two episodes of the sitcom in 2002 and 2003, she certainly left her mark. She not only picked up her first Emmy award for her guest role on the comedy series, but she also received nominations for both appearances.

Now this movie really made news.

In the 2004 comedy Anchorman: The Legend of Ron Burgundy, Applegate plays Veronica Corningstone, a broadcast journalist who works with anchor Ron Burgundy (Will Ferrell) at a San Diego news station in the 1970s. They form a romantic relationship. But after Veronica is promoted to co-anchor, Ron isn't supportive, leading the two to form a fierce rivalry.

The movie—which also stars Paul Rudd, Steve Carell and David Koechner—was such a hit that it led to a 2013 sequel Anchorman 2: The Legend Continues, which Applegate also starred in.

Who wasn't talking about Samantha Who? when the show premiered in 2007?

Applegate played the title character, who suffers amnesia after being involved in a car accident. As she begins to piece her life back together, Samantha realizes she wasn't a nice person and wants to make better choices.

The comedy series ran for two seasons—ending in 2009—with Applegate receiving back-to-back Emmy and Golden Globe nominations for her lead performance.

After meeting and falling hard and fast for each other, Erin (Drew Barrymore) from California and Garrett (Justin Long) from New York decide to enter a long-distance relationship. The 2010 film follows the couple as they navigate the challenges of their new romance, their careers and the opinions of Erin's protective sister Corinne (Applegate) and Garrett's friends Box (Jason Sudeikis) and Dan (Charlie Day).

And it looks like Applegate's friendship with Barrymore truly went the distance.

"I know who she is at the core of who she is for some weird reason, and I think she looks at me and is the same way," she told Tribute Movies in 2010. "There's this feeling of understanding that the two of us have of who we really are deep, deep, deep down where nobody else has seen. And I think that gave us a great chemistry because it was just easy after that. I felt completely protective of her, she felt completely trusting of me, and it just sort of worked."

Oh baby! This comedy had a star-studded cast.

In Up All Night, Applegate plays Reagan, who welcomes a baby girl with her husband Chris (Will Arnett). She returns to the office—where she works with her boss and BFF Ava (Maya Rudolph)—and he stays home with their daughter. The show, which ran from 2011-2012, follows Reagan and Chris as they transition from the life that they knew before having kids to their day-to-day now as new parents and try to balance it all.

Pack your bags and take a trip down memory lane to Applegate's 2015 film Vacation.

A follow-up to the 1983 classic National Lampoon's Vacation, this movie follows a grown-up Rusty Griswold (Ed Helms), who takes his wife Debbie (Applegate) and two kids James (Skyler Gisondo) and Kevin (Steele Stebbins) on a cross-country road trip to the amusement park Walley World, just like he did with his family years ago. However, things don't exactly go according to plan and there are hilarious twists and turns along the way.

The movie is also full of celebrity cameos, including from Chris Hemsworth, Leslie Mann, Regina Hall, Keegan-Michael Key, and, of course, original star Chevy Chase.

Bad Moms? Great movie.

Applegate's Gwendolyn, the PTA mom who appears to have it all together, is a hilarious adversary to Mila Kunis' Amy, who tries to juggle it all and be the "perfect mom." After Gwendolyn's bake sale restrictions push Amy too far, Kunis' character decides to ditch the unrealistic expectations and forms a friendship with fellow moms Carla (Kathryn Hahn) and Kiki (Kristen Bell). Amy runs for PTA president against Gwendolyn and is cheered on by Carla and Kiki. Together, they have some fun and figure out how to better support moms instead of put more pressure on them.

Applegate reprised her role of Gwendolyn for the 2017 sequel A Bad Moms Christmas.

After Applegate's character Jen Harding loses her husband in a hit-and-run car accident, she forms a friendship with Judy Hale (Linda Cardellini), who says she lost her fiancé to a heart attack. However, it soon becomes clears that Judy's past isn't exactly what it seems.

Over the course of its three seasons, Applegate—who is also an executive producer on the series—has received several nominations for her work, including three Emmy nominations and four SAG Award nods. The actress was diagnosed with multiple sclerosis during the final season, and Cardellini recently revealed what it was like for them to film their final scene. 

"We had a really hard time saying goodbye," Cardellini told The Hollywood Reporter. "Jen and Judy, and Linda and Christina were crying some really big tears. I think what you see in the show is that Christina is absolutely as brilliant as she's ever been, and she is just an incredible actress. She can really do it all."

The 29th annual SAG Awards will be broadcast live on Netflix's YouTube channel Sunday, Feb. 26 at 8 p.m. ET/5 p.m. PT.