During her 2018 stint on Celebrity Big Brother U.K., Alley spoke about her former costar Patrick Swayze, whom she developed romantic feelings for while filming the 1985 miniseries North and South.

"I would've loved to have an affair with Patrick Swayze but we were both married so I wouldn't have gone off [with him]," she said.

"I kissed him and I wish I could've had an affair but I'm a strong believer in fidelity and he was married," Alley continued. "When you get on the road and you do a movie, it's very easy to fall in love with your leading man. Very, very easy."

After a handful of other television and film roles throughout the 1980s, the part that really put her on the map was as Rebecca Howe on Cheers. Alley entered the beloved sitcom after Shelley's Long departure, and once told PEOPLE her first weeks on the set were "nerve-racking. They had all created a great series and I didn't particularly want to be the cause of its demise." She wasn't: in the span of six years, she was nominated for five Emmys, winning one.

The 1989 film Look Who's Talking brought together Alley and one of her lifelong friends: John Travolta.

In a 2018 podcast interview, she shared that she fell in love with the actor in the late '80s, but decided not to start a sexual relationship with him because she was married to Parker Stevenson at the time.

"I will say it's one of the hardest things I've ever done, the hardest decision I've ever made because I was madly in love with him — we were fun and funny together," Alley said. "It wasn't a sexual relationship because I'm not going to cheat on my husband. But, you know, I think there are things that are way worse than sexual relationships, than cheating on someone that way. I consider what I did even worse because I actually let myself fall in love with him and stay in love with him for a long time."

Alley won her second Emmy just one year after Cheers for playing devoted mom Sally Goodson in the 1994 television movie David's Mother.

Alley's next big television moment was with a leading role on the 1997 sitcom Veronica's Closet, playing unlucky-in-love lingerie exec Veronica Chase. At the time, Entertainment Weekly said it "gives us the Kirstie Alley we've been wanting — trash-talking and in charge, a strong, mature woman who's both vulnerable to men's charms and sick of their lives."

The show lasted four seasons, earning Alley one more Emmy nomination (plus her sixth Golden Globe nom).

During the height of her fame, much was made about Alley's weight, and she spoke frequently with PEOPLE about her relationship with food — and with herself.

"The weird thing is, I don't like the way I look — and I like who I am," she said in 2004. "I like who I am better than I've ever liked myself."

Her weight was the inspiration behind her 2005 unscripted Showtime series Fat Actress, which ran for one season. In 2006, she appeared on The Oprah Winfrey Show in a bikini to show off her weight loss.

In 2004, she became a spokeswoman for Jenny Craig, stepping away from the brand in 2008 only to come back and lose 50 lbs. on the program in 2015.

In 2004, Alley told PEOPLE she'd been focused on being "the best mother I can be" to kids Lillie and William.

And in 2016, she became a grandmother, after William welcomed son Waylon. She called the news "bliss" while sharing first photos with Twitter followers.

As she continued to pop up in movies and television shows throughout the 2000s, Alley made a solid debut on the 2011 season of Dancing with the Stars.

"I seriously want to do a great job," she said following the season premiere, which paired her with pro Maksim Chmerkovskiy. The pair made it to the finals, coming in second behind Hines Ward and Kym Johnson.

"When I look at what evolved from the first day to now, it's extraordinary," said Alley, who also opened up about her weight loss during the season. "It sort of gave me a new view of what I wanted to do in my life."

Alley stirred up several controversies on social media, with tweets questioning the #MeToo movement and supporting Donald Trump, and more recently, a tweet wondering "what's real or what is fake" about the war in Ukraine.

A long-time Scientologist, she also spoke out after Leah Remini left and dropped her own bombshells about the church, telling Howard Stern, "When you decide to blanket statement, 'Scientology is evil,' you are my enemy."

Alley continued to stay busy in the years after DWTS, trying another self-referential sitcom, 2013's Kirstie, plus stints on Hot in Cleveland and Scream Queens. In 2022, she took a turn on The Masked Singer, making it to the semi-finals.

Alley's second-to-last film credit was a sentimental one: a 2019 cameo on The Goldbergs alongside Cheers costars Rhea Perlman, John Ratzenberger and George Wendt.

On Dec. 5, 2022, Alley's children announced that the actress had died at the age of 71. Her rep later confirmed she'd recently been diagnosed with colon cancer.

"We are sad to inform you that our incredible, fierce and loving mother has passed away after a battle with cancer, only recently discovered," they said in a statement.

"She was surrounded by her closest family and fought with great strength, leaving us with a certainty of her never-ending joy of living and whatever adventures lie ahead," they continued. "As iconic as she was on screen, she was an even more amazing mother and grandmother."

The siblings remembered their mother's "zest and passion for life, her children, grandchildren and her many animals, not to mention her eternal joy of creating, were unparalleled and leave us inspired to live life to the fullest just as she did."

They also thanked the "incredible team of doctors and nurses" at the Moffitt Cancer Center.

The statement concludes with True and Lillie thanking Alley's fans, sharing, "We thank you for your love and prayers and ask that you respect our privacy at this difficult time."