What about Tina Turner? She spent 20 years willingly taking a backseat to Ike (even though she was definitely the bigger star of the pair), and let him drag her down with him during the mid-70s as he descended into a drug, alcohol & ego fueled tailspin. Finally, after dumping his ass, she got left with literarlly nothing but her stage name “Tina Turner” - no royalties or rights, even for the songs she wrote, and not a cent. But she clawed her way back to the top - eventually recording a grammy-winning album, a string of top ten hits, and establishing herself as one of the most influential female singers in the history of rock music. Now that’s what I call a comeback story!
I was going to say child stars could be it’s whole own little sub category. My vote:
Neil Patrick Harris. Kind of fell off the radar after Doogie Howser but after playing himself in Harold and Kumar he’s been getting more and more buzz each year with HIMYM, H&K2, Dr Horrible, Emmy hosting, SNL, various websites (NPH Fuck Yeah) etc, despite being openly gay.
I always confuse him with Jackie Coogan, who is remembered mostly for three things:
- The highly acclaimed child star of The Kid (1921).
- Having his vast earnings frittered away by his parents, with the results that children working in Hollywood now must have “Coogan Accounts” set up for them.
- Playing Uncle Fester in The Addams Family (1964-66).
It might be considered a comeback story in that his best-known roles were 40 years apart, but he actually had a pretty solid list of credits in between.
Appearing in Quentin Tarantino movies tends to do this to actors. Pam Grier and Robert Forster just to name two.
Catherine Zeta Jones was doing mobile phone commercials back when she was still a hot property.
Odesio
Harvey Keitel was sort of low profile in the '80s. High profile in the '70s and '90s.
Yes yes. I no longer subscribe to my original stance of commercials. Drew Barrymore is the answer to this thread and she’s appearing in commercials too.
Though this means my nomination of Charlie Sheen is in good standing again. 
How about a comeback couple - Goldie Hawn and Kurt Russell.
Hawn played a ditzy girl on Laugh-In and in her early movies. But rather than fade away when she outgrew those roles she was able to move on to female lead roles.
Russell was a teenage star in Disney movies. But when he outgrew those he was able to move into action movies with some occasional dramatic roles.
Thats one of the comebacks that I really like seeing.
Whoda thunk it? From Kelly Leek “You like Harleys Huh? I got a Harley.”
To Freddie Kruger. Way to go Jackie!
Since there’s a belated Harve Presnell obituary thread open I’ll mention him.
He was fairly big in the '60s, mainly in The Unsinkable Molly Brown and Paint Your Wagon (his recording of “They Call the Wind Maria” was a big hit). Then he left Hollywood to do everything from West End to Broadway to regional dinner theater and road shows for almost thirty years (just a smattering of very minor credits twixt '69 and '96) and then comes back bigger than he’s ever been on screen with plum character roles in Fargo, Saving Private Ryan and constant guest shots and character roles for the last decade of his life.
Well, yes and no. She doesn’t really meet the OPs qualifications, but she was A list for her genre back in the day, and seems to have successfully reinvented herself
It’s like she keeps going in and out of popularity. 
Vanessa L. Williams
first woman of African American descent to be crowned Miss America
resignation due to scandal involving nude (beautiful) pictures
rebounds with multiple Grammy Award nominations
nominated for a Tony Award in 2002
repeated nominations for an Emmy Award
Plays Wilhelmina Slater on Ugly Betty.
You cannot talk about a resurrected acting career without mentioning one of the first: Buster Keaton. Silent slapstick genius on par with Chaplin that practically disappeared from the public’s eye when he signed with MGM in the late 1920s. His career was resurrected 20 years when critics finally acknowledged his technical skills during his silent era. Throughout the 1950s, his career was revived until his death in 1966.
How about George Burns? After Gracie died, he disappeared from view, then came back to win an Oscar for “The Sunshine Boys”.
Neil Patrick Harris
Yeah, but for a while her career was really going down.
Didn’t Jessica Tandy have a long period of not working?
Diana Muldaur was never a huge star, but she retired rather young. She returned to TV in the 80s for Star Trek TNG, then had a huge role on LA Law.
Yeah. I find it hilarious that Doogie Howser is cool now.
She didn’t stop working entirely in film and TV, but, if you look at her IMDB profile:
- 36 acting credits from 1939 through 1959
- Only 6 acting credits from 1960 through 1980 (three of which were single TV episodes)
- 19 acting credits from 1981 through 1994, when she passed away.
My understanding is that, during the 1960s and 1970s, she (and her husband Hume Cronyn) focused on stage work; she won a Tony in 1977.
Hume Cronyn was her husband? I did not know that.